Polyamines Papers

Here are listed papers either about polyamines or that mentioned the foundation in the acknowledgments.


  • [DOI] C. R. Schultz, C. P. Bupp, S. Rajasekaran, and A. S. Bachmann, “Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation,” Biochemical journal, vol. 476, iss. 14, pp. 2047-2057, 2019.
    author = {Schultz, Chad R. and Bupp, Caleb P. and Rajasekaran, Surender and Bachmann, André S.},
    title = "{Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation}",
    journal = {Biochemical Journal},
    volume = {476},
    number = {14},
    pages = {2047-2057},
    year = {2019},
    month = {07},
    abstract = "{We recently described a new autosomal dominant genetic disorder in a pediatric patient caused by a heterozygous de novo mutation in the ornithine decarboxylase 1 (ODC1) gene. The new genetic disorder is characterized by global developmental delay, alopecia, overgrowth, and dysmorphic features. We hypothesized that this new mutation (c.1342 A\\>T) leads to a C-terminal truncation variant of the ODC protein that is resistant to normal proteasomal degradation, leading to putrescine accumulation in cells. ODC (E.C. is a rate-limiting enzyme in the biosynthesis of polyamines (putrescine, spermidine, and spermine) that plays a crucial role during embryogenesis, organogenesis, and tumorigenesis. In this study, we show that primary dermal fibroblasts derived from a skin biopsy of a 3-year-old patient contain large amounts of ODC protein and putrescine compared with primary dermal (neonatal and adult) fibroblast control cells. Importantly, the accumulated ODC protein variant remained functionally active as we detected exceptionally high ODC enzyme activity in both primary dermal fibroblasts (12–17-fold of controls) and red blood cells (RBCs) (125–137-fold of controls), using a specific 14C radioactive ODC activity assay. Exposure of primary dermal fibroblasts to ODC inhibitor α-difluoromethylornithine (DFMO) reduced the ODC activity and putrescine to levels observed in controls without adversely affecting cell morphology or inducing cell death. In conclusion, our patient and potentially other patients that carry a similar ODC1 gain-of-function mutation might benefit from treatment with DFMO, a drug with a good safety profile, to suppress the exceptionally high ODC activity and putrescine levels in the body.}",
    issn = {0264-6021},
    doi = {10.1042/BCJ20190294},
    url = {https://doi.org/10.1042/BCJ20190294},
    eprint = {https://portlandpress.com/biochemj/article-pdf/476/14/2047/850421/bcj-2019-0294.pdf},
  • M. R. Mooney, D. Geerts, E. J. Kort, and A. S. Bachmann, “Anti-tumor effect of sulfasalazine in neuroblastoma.,” Biochemical pharmacology, vol. 162, pp. 237-249, 2019.
    title={Anti-tumor effect of sulfasalazine in neuroblastoma.},
    author={Marie R Mooney and Dirk Geerts and Eric J. Kort and Andr{\'e} S Bachmann},
    journal={Biochemical pharmacology},
  • [DOI] C. L. Stump, R. P. Feehan, T. Jordan, L. M. Shantz, and S. L. Nowotarski, “Knocking down raptor in human keratinocytes affects ornithine decarboxylase in a post-transcriptional manner following ultraviolet b exposure,” Amino acids, 2019.
    author={Stump, Coryn L.
    and Feehan, Robert P.
    and Jordan, Torey
    and Shantz, Lisa M.
    and Nowotarski, Shannon L.},
    title={Knocking down raptor in human keratinocytes affects ornithine decarboxylase in a post-transcriptional Manner following ultraviolet B exposure},
    journal={Amino Acids},
    abstract={Non-melanoma skin cancer (NMSC) is the most common form of cancer. Ultraviolet-B (UVB) radiation has been shown to be a complete carcinogen in the development of NMSC. The mammalian target of rapamycin complex 1 (mTORC1) is upregulated by UVB. Ornithine decarboxylase (ODC), the first enzyme of the polyamine biosynthetic pathway, is also upregulated in response to UVB. However, the interplay between these two pathways after UVB exposure remains unclear. The studies described here compare mRNA stability between normal human keratinocytes (HaCaT cells) and HaCaT cells with low levels of raptor to investigate whether the induction of ODC by UVB is dependent on mTORC1. We show that the knockdown of mTORC1 activity led to decreased levels of ODC protein both before and after exposure to 20?mJ/cm2 UVB. ODC mRNA was less stable in cells with decreased mTORC1 activity. Polysome profiles revealed that the initiation of ODC mRNA translation did not change in UVB-treated cells. We have shown that the ODC transcript is stabilized by the RNA-binding protein human antigen R (HuR). To expand these studies, we investigated whether HuR functions to regulate ODC mRNA stability in human keratinocytes exposed to UVB. We show an increased cytoplasmic localization of HuR after UVB exposure in wild-type cells. The ablation of HuR via CRISPR/Cas9 did not alter the stability of the ODC message, suggesting the involvement of other trans-acting factors. These data suggest that in human keratinocytes, ODC mRNA stability is regulated, in part, by an mTORC1-dependent mechanism after UVB exposure.},


  • [DOI] A. Arruabarrena-Aristorena, A. Zabala-Letona, and A. Carracedo, “Oil for the cancer engine: the cross-talk between oncogenic signaling and polyamine metabolism,” Science advances, vol. 4, iss. 1, p. eaar2606-eaar2606, 2018.
    author={Arruabarrena-Aristorena, Amaia
    and Zabala-Letona, Amaia
    and Carracedo, Arkaitz},
    title={Oil for the cancer engine: The cross-talk between oncogenic signaling and polyamine metabolism},
    journal={Science advances},
    publisher={American Association for the Advancement of Science},
    keywords={Chromatin Assembly and Disassembly},
    keywords={*Signal Transduction},
    abstract={The study of metabolism has provided remarkable information about the biological basis and therapeutic weaknesses of cancer cells. Classic biochemistry established the importance of metabolic alterations in tumor biology and revealed the importance of various metabolite families to the tumorigenic process. We have evidence of the central role of polyamines, small polycatonic metabolites, in cell proliferation and cancer growth from these studies. However, how cancer cells activate this metabolic pathway and the molecular cues behind the oncogenic action of polyamines has remained largely obscure. In contrast to the view of metabolites as fuel (anabolic intermediates) for cancer cells, polyamines are better defined as the oil that lubricates the cancer engine because they affect the activity of biological processes. Modern research has brought back to the limelight this metabolic pathway, providing a strong link between genetic, metabolic, and signaling events in cancer. In this review, we enumerate and discuss current views of the regulation and activity of polyamine metabolism in tumor cell biology.},
  • [DOI] N. Mart{‘i}n-Mart{‘i}n, A. Zabala-Letona, S. Fernández-Ruiz, L. Arreal, L. Camacho, M. Castillo-Martin, A. R. Cortazar, V. Torrano, I. Astobiza, P. Zúñiga-Garc{‘i}a, A. Ugalde-Olano, A. Loizaga-Iriarte, M. Unda, L. Valcárcel-Jiménez, A. Arruabarrena-Aristorena, M. Piva, P. Sánchez-Mosquera, A. M. Aransay, A. Gomez-Muñoz, R. Barrio, J. D. Sutherland, and A. Carracedo, “Pparδ elicits ligand-independent repression of trefoil factor family to limit prostate cancer growth,” Cancer research, vol. 78, iss. 2, p. 399–409, 2018.
    @article {Mart{\'\i}n-Mart{\'\i}n399,
    author = {Mart{\'\i}n-Mart{\'\i}n, Natalia and Zabala-Letona, Amaia and Fern{\'a}ndez-Ruiz, Sonia and Arreal, Leire and Camacho, Laura and Castillo-Martin, Mireia and Cortazar, Ana R. and Torrano, Ver{\'o}nica and Astobiza, Ianire and Z{\'u}{\~n}iga-Garc{\'\i}a, Patricia and Ugalde-Olano, Aitziber and Loizaga-Iriarte, Ana and Unda, Miguel and Valc{\'a}rcel-Jim{\'e}nez, Lorea and Arruabarrena-Aristorena, Amaia and Piva, Marco and S{\'a}nchez-Mosquera, Pilar and Aransay, Ana M. and Gomez-Mu{\~n}oz, Antonio and Barrio, Rosa and Sutherland, James D. and Carracedo, Arkaitz},
    title = {PPARδ Elicits Ligand-Independent Repression of Trefoil Factor Family to Limit Prostate Cancer Growth},
    volume = {78},
    number = {2},
    pages = {399--409},
    year = {2018},
    doi = {10.1158/0008-5472.CAN-17-0908},
    publisher = {American Association for Cancer Research},
    abstract = {The nuclear receptor PPAR-β/δ (PPARD) has essential roles in fatty acid catabolism and energy homeostasis as well as cell differentiation, inflammation, and metabolism. However, its contributions to tumorigenesis are uncertain and have been disputed. Here, we provide evidence of tumor suppressive activity of PPARD in prostate cancer through a noncanonical and ligand-independent pathway. PPARD was downregulated in prostate cancer specimens. In murine prostate epithelium, PPARD gene deletion resulted in increased cellularity. Genetic modulation of PPARD in human prostate cancer cell lines validated the tumor suppressive activity of this gene in vitro and in vivo. Mechanistically, PPARD exerted its activity in a DNA binding-dependent and ligand-independent manner. We identified a novel set of genes repressed by PPARD that failed to respond to ligand-mediated activation. Among these genes, we observed robust regulation of the secretory trefoil factor family (TFF) members, including a causal and correlative association of TFF1 with prostate cancer biology in vitro and in patient specimens. Overall, our results illuminate the oncosuppressive function of PPARD and understanding of the pathogenic molecular pathways elicited by this nuclear receptor.Significance: These findings challenge the presumption that the function of the nuclear receptor PPARβ/δ in cancer is dictated by ligand-mediated activation. Cancer Res; 78(2); 399{\textendash}409. {\textcopyright}2017 AACR.},
    issn = {0008-5472},
    URL = {https://cancerres.aacrjournals.org/content/78/2/399},
    eprint = {https://cancerres.aacrjournals.org/content/78/2/399.full.pdf},
    journal = {Cancer Research}
  • [DOI] L. Camacho, A. Zabala-Letona, and A. Carracedo, “Re-evaluating statin activity in cancer,” Aging, vol. 10, iss. 7, pp. 1538-1539, 2018.
    @article {IMA:IMA2,
    author = {Camacho, Laura and Zabala-Letona, Amaia and Carracedo, Arkaitz},
    title = {Re-evaluating statin activity in cancer},
    journal = {Aging},
    volume = {10},
    number = {7},
    publisher = {Impact Journals, LLC},
    issn = {1945-4589},
    url = {https://doi.org/10.18632/aging.101504},
    doi = {10.18632/aging.101504},
    pages = {1538-1539},
    year = {2018},
  • [DOI] A. S. Bachmann and D. Geerts, “Polyamine synthesis as a target of myc oncogenes,” Journal of biological chemistry, vol. 293, iss. 48, pp. 18757-18769, 2018.
    author = {Bachmann, André S. and Geerts, Dirk},
    title = {Polyamine synthesis as a target of MYC oncogenes},
    volume = {293},
    number = {48},
    pages = {18757-18769},
    year = {2018},
    doi = {10.1074/jbc.TM118.003336},
    abstract ={This paper is in recognition of the 100th birthday of Dr. Herbert Tabor, a true pioneer in the polyamine field for over 70 years, who served as the editor-in-chief of the Journal of Biological Chemistry from 1971 to 2010. We review current knowledge of MYC proteins (c-MYC, MYCN, and MYCL) and focus on ornithine decarboxylase 1 (ODC1), an important bona fide gene target of MYC, which encodes the sentinel, rate-limiting enzyme in polyamine biosynthesis. Although notable advances have been made in designing inhibitors against the “undruggable” MYCs, their downstream targets and pathways are currently the main avenue for therapeutic anticancer interventions. To this end, the MYC–ODC axis presents an attractive target for managing cancers such as neuroblastoma, a pediatric malignancy in which MYCN gene amplification correlates with poor prognosis and high-risk disease. ODC and polyamine levels are often up-regulated and contribute to tumor hyperproliferation, especially of MYC-driven cancers. We therefore had proposed to repurpose α-difluoromethylornithine (DFMO), an FDA-approved, orally available ODC inhibitor, for management of neuroblastoma, and this intervention is now being pursued in several clinical trials. We discuss the regulation of ODC and polyamines, which besides their well-known interactions with DNA and tRNA/rRNA, are involved in regulating RNA transcription and translation, ribosome function, proteasomal degradation, the circadian clock, and immunity, events that are also controlled by MYC proteins.},
    URL = {http://www.jbc.org/content/293/48/18757.abstract},
    eprint = {http://www.jbc.org/content/293/48/18757.full.pdf+html},
    journal = {Journal of Biological Chemistry}
  • [DOI] C. P. Bupp, C. R. Schultz, K. L. Uhl, S. Rajasekaran, and A. S. Bachmann, “Novel de novo pathogenic variant in the odc1 gene in a girl with developmental delay, alopecia, and dysmorphic features,” American journal of medical genetics part a, vol. 176, iss. 12, pp. 2548-2553, 2018.
    author = {Bupp, Caleb P. and Schultz, Chad R. and Uhl, Katie L. and Rajasekaran, Surender and Bachmann, André S.},
    title = {Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features},
    journal = {American Journal of Medical Genetics Part A},
    volume = {176},
    number = {12},
    pages = {2548-2553},
    keywords = {alopecia, DFMO, new pediatric developmental disorder, ODC c-terminal truncation, whole-exome sequencing},
    doi = {10.1002/ajmg.a.40523},
    url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.40523},
    eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.40523},
    abstract = {The ornithine decarboxylase 1 (ODC1) gene plays an important role in physiological and cell developmental processes including embryogenesis, organogenesis, and neoplastic cell growth. Here, we report an 32-month-old Caucasian female with a heterozygous de novo nonsense mutation in the ODC1 gene that leads to a premature abrogation of 14-aa residues at the ODC protein c-terminus. This is the first human case confirming similar symptoms observed in a transgenic ODC1 mouse model first described over 20 years ago. Phenotypic manifestations include macrosomia, macrocephaly, developmental delay, alopecia, spasticity, hypotonia, cutaneous vascular malformation, delayed visual maturation, and sensorineural hearing loss. We here describe for the first time a new pediatric disorder that is directly linked to a de novo pathogenic variant in the ODC1 gene. The ODC1 gene mutation (c.1342 A>T) was identified by whole-exome sequencing and confirmed by Sanger sequencing. Red blood cells obtained from our patient showed elevated ODC protein and polyamine levels compared to healthy controls. Our autosomal dominant patient who carries this gain-of-function ODC1 mutation may benefit from treatment with α-difluoromethylornithine, a well-tolerated, U.S. Food and Drug Administration (FDA). FDA-approved drug.},
    year = {2018}
  • [DOI] M. R. PIERCE, N. A. BAKAS, M. C. PIRRUNG, and A. S. BACHMANN, “Thiasyrbactins induce cell death via proteasome inhibition in multiple myeloma cells,” Anticancer research, vol. 38, iss. 10, pp. 5607-5613, 2018.
    title = {Thiasyrbactins Induce Cell Death via Proteasome Inhibition in Multiple Myeloma Cells},
    volume = {38},
    number = {10},
    pages = {5607-5613},
    year = {2018},
    doi = {10.21873/anticanres.12895},
    abstract ={Background/Aim: Proteasome inhibition is a validated therapeutic strategy for the treatment of refractory and relapsed multiple myeloma (MM) and mantle cell lymphoma. We previously showed that thiasyrbactins (NAM compounds) are inhibitors with an affinity for the trypsin-like (T-L, β2) site of the constitutive proteasome, and more profoundly for the T-L site of the immunoproteasome. Materials and Methods: In this study, the biological activity of three NAM compounds was evaluated using four MM cell lines (ARD, U266, MM1R, and MM1S). We assessed the effect of (NAM-93, NAM-95, and NAM-105 on cell viability, as well as cell-based proteasomal activities, and determined the EC50 and Ki50 values, respectively. Results: MM cells were most sensitive to NAM-93 with EC50 values <0.75 μM after 48 h of treatment. NAM-105 had a similar profile in most of the MM cells with EC50 values ranging between 0.42 and 3.02 μM. The level of inhibition of the proteasome T-L sub-catalytic activity in actively-growing MM cells was similar for NAM-93 and NAM-105. However, in each cell line, NAM-93 was more effective than NAM-105 at inhibiting overall trypsin-like sub-catalytic activity while NAM-105 was typically more effective at inhibiting overall chymotrypsin-like (CT-L, β5) sub-catalytic activity. Conclusion: These results show for the first time the proteasome-targeted biological activity of thiasyrbactins in MM tumor cells.},
    URL = {http://ar.iiarjournals.org/content/38/10/5607.abstract},
    eprint = {http://ar.iiarjournals.org/content/38/10/5607.full.pdf+html},
    journal = {Anticancer Research}
  • [DOI] R. R. Weicht, C. R. Schultz, D. Geerts, K. L. Uhl, and A. S. Bachmann, "Polyamine biosynthetic pathway as a drug target for osteosarcoma therapy," Medical sciences, vol. 6, iss. 3, 2018.
    AUTHOR = {Weicht, Rebecca R. and Schultz, Chad R. and Geerts, Dirk and Uhl, Katie L. and Bachmann, André S.},
    TITLE = {Polyamine Biosynthetic Pathway as a Drug Target for Osteosarcoma Therapy},
    JOURNAL = {Medical Sciences},
    VOLUME = {6},
    YEAR = {2018},
    NUMBER = {3},
    ARTICLE-NUMBER = {65},
    URL = {https://www.mdpi.com/2076-3271/6/3/65},
    PubMedID = {30115881},
    ISSN = {2076-3271},
    ABSTRACT = {Osteosarcoma (OS) is the most common bone tumor in children. Polyamines (PAs) are ubiquitous cations involved in many cell processes including tumor development, invasion and metastasis. In other pediatric cancer models, inhibition of the PA biosynthesis pathway with ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) results in decreased cell proliferation and differentiation. In OS, the PA pathway has not been evaluated. DFMO is an attractive, orally administered drug, is well tolerated, can be given for prolonged periods, and is already used in pediatric patients. Three OS cell lines were used to study the cellular effects of PA inhibition with DFMO: MG-63, U-2 OS and Saos-2. Effects on proliferation were analyzed by cell count, flow cytometry-based cell cycle analysis and RealTime-Glo™ MT Cell Viability assays. Intracellular PA levels were measured with high-performance liquid chromatography (HPLC). Western blot analysis was used to evaluate cell differentiation. DFMO exposure resulted in significantly decreased cell proliferation in all cell lines. After treatment, intracellular spermidine levels were drastically decreased. Cell cycle arrest at G2/M was observed in U-2 OS and Saos-2. Cell differentiation was most prominent in MG-63 and U-2 OS as determined by increases in the terminal differentiation markers osteopontin and collagen 1a1. Cell proliferation continued to be suppressed for several days after removal of DFMO. Based on our findings, DFMO is a promising new adjunct to current osteosarcoma therapy in patients at high risk of relapse, such as those with poor necrosis at resection or those with metastatic or recurrent osteosarcoma. It is a well-tolerated oral drug that is currently in phase II clinical trials in pediatric neuroblastoma patients as a maintenance therapy. The same type of regimen may also improve outcomes in osteosarcoma patients in whom there have been essentially no medical advances in the last 30 years.},
    DOI = {10.3390/medsci6030065}
  • [DOI] K. L. Uhl, C. R. Schultz, D. Geerts, and A. S. Bachmann, "Harmine, a dual-specificity tyrosine phosphorylation-regulated kinase (dyrk) inhibitor induces caspase-mediated apoptosis in neuroblastoma," Cancer cell international, vol. 18, pp. 82-82, 2018.
    author={Uhl, Katie L.
    and Schultz, Chad R.
    and Geerts, Dirk
    and Bachmann, Andr{\'e} S.},
    title={Harmine, a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) inhibitor induces caspase-mediated apoptosis in neuroblastoma},
    journal={Cancer cell international},
    publisher={BioMed Central},
    keywords={Molecular docking},
    keywords={Natural products},
    abstract={BACKGROUND: Neuroblastoma (NB) is an early childhood malignancy that arises from the developing sympathetic nervous system. Harmine is a tricyclic b-carboline alkaloid isolated from the harmal plant that exhibits both cytostatic and cytotoxic effects. Harmine is capable of blocking the activities of dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family proteins and mitogen-activated protein kinase. These kinases promote proliferation and inhibit apoptosis. METHODS: Four human NB cell lines were used to study the effects of harmine treatment: SKNBE and KELLY (MYCN-amplified) as well as SKNAS and SKNFI (MYCN non-amplified). The anti-cancer properties of harmine were examined by RealTime-Glo MT cell viability assays, caspase activity assays, PARP cleavage using Western blot analysis, and flow cytometry-based Annexin V detection. A molecular interaction model of harmine bound to the DYRK2 family kinase was generated by computational docking using X-ray structures. NB tumors from human patients were profiled for DYRK mRNA expression patterns and clinical correlations using the R2 platform. RESULTS: The IC(50) values for harmine after 72?h treatment were 169.6, 170.8, and 791.7?mM for SKNBE, KELLY, and SKNFI, respectively. Exposure of these NB cell lines to 100?mM of harmine resulted in caspase-3/7 and caspase-9 activation as well as caspase-mediated PARP cleavage and Annexin V-positive stained cells, as early as 24?h after treatment, clearly suggesting apoptosis induction, especially in MYCN-amplified cell lines. Elevated DYRK2 mRNA levels correlated with poor prognosis in a large cohort of NB tumors. CONCLUSION: Harmine is a known inhibitor of DYRK family kinases. It can induce apoptosis in NB cell lines, which led us to investigate the clinical correlations of DYRK family gene expression in NB tumors. The patient results support our hypothesis that DYRK inhibition by harmine and the subsequent triggering of caspase-mediated apoptosis might present a novel approach to NB therapy.},
  • [DOI] C. R. Schultz, D. Geerts, M. Mooney, R. El-Khawaja, J. Koster, and A. S. Bachmann, "Synergistic drug combination GC7/DFMO suppresses hypusine/spermidine-dependent eIF5A activation and induces apoptotic cell death in neuroblastoma," Biochemical journal, vol. 475, iss. 2, pp. 531-545, 2018.
    author = {Schultz, Chad R. and Geerts, Dirk and Mooney, Marie and El-Khawaja, Raid and Koster, Jan and Bachmann, André S.},
    title = "{Synergistic drug combination GC7/DFMO suppresses hypusine/spermidine-dependent eIF5A activation and induces apoptotic cell death in neuroblastoma}",
    journal = {Biochemical Journal},
    volume = {475},
    number = {2},
    pages = {531-545},
    year = {2018},
    month = {01},
    abstract = "{The eukaryotic initiation factor 5A (eIF5A), which contributes to several crucial processes during protein translation, is the only protein that requires activation by a unique post-translational hypusine modification. eIF5A hypusination controls cell proliferation and has been linked to cancer. eIF5A hypusination requires the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase and uniquely depends on the polyamine (PA) spermidine as the sole substrate. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in PA biosynthesis. Both ODC and PAs control cell proliferation and are frequently dysregulated in cancer. Since only spermidine can activate eIF5A, we chose the hypusine–PA nexus as a rational target to identify new drug combinations with synergistic antiproliferative effects. We show that elevated mRNA levels of the two target enzymes DHPS and ODC correlate with poor prognosis in a large cohort of neuroblastoma (NB) tumors. The DHPS inhibitor GC7 (N1-guanyl-1,7-diaminoheptane) and the ODC inhibitor α-difluoromethylornithine (DFMO) are target-specific and in combination induced synergistic effects in NB at concentrations that were not individually cytotoxic. Strikingly, while each drug alone at higher concentrations is known to induce p21/Rb- or p27/Rb-mediated G1 cell cycle arrest, we found that the drug combination induced caspase 3/7/9, but not caspase 8-mediated apoptosis, in NB cells. Hypusinated eIF5A levels and intracellular spermidine levels correlated directly with drug treatments, signifying specific drug targeting effects. This two-pronged GC7/DFMO combination approach specifically inhibits both spermidine biosynthesis and post-translational, spermidine-dependent hypusine-eIF5A activation, offering an exciting clue for improved NB drug therapy.}",
    issn = {0264-6021},
    doi = {10.1042/BCJ20170597},
    url = {https://doi.org/10.1042/BCJ20170597},
    eprint = {https://portlandpress.com/biochemj/article-pdf/475/2/531/692551/bcj-2017-0597.pdf},
  • [DOI] N. A. Bakas, C. R. Schultz, L. P. Yco, C. C. Roberts, C. A. Chang, A. S. Bachmann, and M. C. Pirrung, "Immunoproteasome inhibition and bioactivity of thiasyrbactins," Bioorganic & medicinal chemistry, vol. 26, iss. 2, pp. 401-412, 2018.
    title = "Immunoproteasome inhibition and bioactivity of thiasyrbactins",
    journal = "Bioorganic & Medicinal Chemistry",
    volume = "26",
    number = "2",
    pages = "401 - 412",
    year = "2018",
    issn = "0968-0896",
    doi = "https://doi.org/10.1016/j.bmc.2017.11.048",
    url = "http://www.sciencedirect.com/science/article/pii/S0968089617318710",
    author = "Nicole A. Bakas and Chad R. Schultz and Lisette P. Yco and Christopher C. Roberts and Chia-en A. Chang and André S. Bachmann and Michael C. Pirrung",
    keywords = "Proteasome, Macrolactam, Conformational analysis, Trypsin-like site, Neuroblastoma",
    abstract = "A family of macrodilactam natural products, the syrbactins, are known proteasome inhibitors. A small group of syrbactin analogs was prepared with a sulfur-for-carbon substitution to enhance synthetic accessibility and facilitate modulation of their solubility. Two of these compounds surprisingly proved to be inhibitors of the trypsin-like catalytic site, including of the immunoproteasome. Their bound and free conformations suggest special properties of the thiasyrbactin ring are responsible for this unusual preference, which may be exploited to develop drug-like immunoproteasome inhibitors. These compounds show greater selectivity than earlier compounds used to infer phenotypes of immunoproteasome inhibition, like ONX-0914."
  • [DOI] F. W. Bazer, R. C. Burghardt, G. A. Johnson, T. E. Spencer, and G. Wu, "Mechanisms for the establishment and maintenance of pregnancy: synergies from scientific collaborations†," Biology of reproduction, vol. 99, iss. 1, pp. 225-241, 2018.
    author = {Bazer, Fuller W and Burghardt, Robert C and Johnson, Gregory A and Spencer, Thomas E and Wu, Guoyao},
    title = "{Mechanisms for the establishment and maintenance of pregnancy: synergies from scientific collaborations†}",
    journal = {Biology of Reproduction},
    volume = {99},
    number = {1},
    pages = {225-241},
    year = {2018},
    month = {02},
    abstract = "{Research on the functions of interferon tau (IFNT) led to the theory of pregnancy recognition signaling in ruminant species. But IFNT does much more as it induces expression of interferon regulatory factor 2 (IRF2) in uterine luminal (LE), superficial glandular (sGE), but not glandular (GE) epithelia. First, IRF2 silences transcription of the estrogen receptor alpha gene and, indirectly, transcription of the oxytocin receptor gene to abrogate development of the luteolytic mechanism to prevent regression of the corpus luteum and its production of progesterone for establishing and maintaining pregnancy. Second, IRF2 silences expression of classical interferon-stimulated genes in uterine LE and sGE; however, uterine LE and sGE respond to progesterone (P4) and IFNT to increase expression of genes for transport of nutrients into the uterine lumen such as amino acids and glucose. Other genes expressed by uterine LE and sGE encode for adhesion molecules such as galectin 15, cathepsins, and cystatins for tissue remodeling, and hypoxia-inducible factor relevant to angiogenesis and survival of blastocysts in a hypoxic environment. IFNT is also key to a servomechanism that allows uterine epithelia, particularly GE, to proliferate and to express genes in response to placental lactogen and placental growth hormone in sheep. The roles of secreted phosphoprotein 1 are also discussed regarding its role in implantation in sheep and pigs, as well as its stimulation of expression of mechanistic target of rapamycin mRNA and protein which is central to proliferation, migration, and gene expression in the trophectoderm cells.}",
    issn = {0006-3363},
    doi = {10.1093/biolre/ioy047},
    url = {https://doi.org/10.1093/biolre/ioy047},
    eprint = {http://oup.prod.sis.lan/biolreprod/article-pdf/99/1/225/25155115/ioy047.pdf},
  • [DOI] H. L. Chan, F. Beckedorff, Y. Zhang, J. Garcia-Huidobro, H. Jiang, A. Colaprico, D. Bilbao, M. E. Figueroa, J. LaCava, R. Shiekhattar, and L. Morey, "Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms," Nature communications, vol. 9, iss. 1, p. 3377, 2018.
    author={Chan, Ho Lam
    and Beckedorff, Felipe
    and Zhang, Yusheng
    and Garcia-Huidobro, Jenaro
    and Jiang, Hua
    and Colaprico, Antonio
    and Bilbao, Daniel
    and Figueroa, Maria E.
    and LaCava, John
    and Shiekhattar, Ramin
    and Morey, Lluis},
    title={Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms},
    journal={Nature Communications},
    abstract={Polycomb repressive complex 1 (PRC1) plays essential roles in cell fate decisions and development. However, its role in cancer is less well understood. Here, we show that RNF2, encoding RING1B, and canonical PRC1 (cPRC1) genes are overexpressed in breast cancer. We find that cPRC1 complexes functionally associate with ERa and its pioneer factor FOXA1 in ER+ breast cancer cells, and with BRD4 in triple-negative breast cancer cells (TNBC). While cPRC1 still exerts its repressive function, it is also recruited to oncogenic active enhancers. RING1B regulates enhancer activity and gene transcription not only by promoting the expression of oncogenes but also by regulating chromatin accessibility. Functionally, RING1B plays a divergent role in ER+ and TNBC metastasis. Finally, we show that concomitant recruitment of RING1B to active enhancers occurs across multiple cancers, highlighting an under-explored function of cPRC1 in regulating oncogenic transcriptional programs in cancer.},
  • [DOI] S. L. Nowotarski, R. P. Feehan, C. Presloid, and L. M. Shantz, "Knockout of raptor destabilizes ornithine decarboxylase mrna and decreases binding of hur to the odc transcript in cells exposed to ultraviolet-b irradiation," Biochemical and biophysical research communications, vol. 505, iss. 4, pp. 1022-1026, 2018.
    title = "Knockout of Raptor destabilizes ornithine decarboxylase mRNA and decreases binding of HuR to the ODC transcript in cells exposed to ultraviolet-B irradiation",
    journal = "Biochemical and Biophysical Research Communications",
    volume = "505",
    number = "4",
    pages = "1022 - 1026",
    year = "2018",
    issn = "0006-291X",
    doi = "https://doi.org/10.1016/j.bbrc.2018.10.019",
    url = "http://www.sciencedirect.com/science/article/pii/S0006291X18321612",
    author = "Shannon L. Nowotarski and Robert P. Feehan and Christopher Presloid and Lisa M. Shantz",
    keywords = "ODC, UVB, HuR, mTORC1, Non-melanoma skin cancer",
    abstract = "Non-melanoma skin cancer (NMSC) is the most commonly diagnosed cancer in the United States. Ultraviolet-B (UVB) irradiation is the primary carcinogen responsible for stimulating NMSC development. Ornithine Decarboxylase (ODC), the first rate-limiting enzyme in the synthesis of polyamines, is upregulated in response to a variety of proliferation stimuli, including UVB exposure. Our previous studies have demonstrated regulation of ODC synthesis by the mammalian target of rapamycin complex 1 (mTORC1) in cells transformed by oncogenic Ras. The goal of these studies was to better understand the link between mTORC1 and ODC in nontransformed cells treated with UVB. We show that the ablation of mTORC1 activity by conditional knockout of its essential component Raptor led to decreased levels of ODC protein both before and after exposure to 10 mJ/cm2 UVB. Moreover, ODC mRNA was destabilized in the absence of Raptor, suggesting post-transcriptional regulation. We have previously shown that the ODC transcript is stabilized by the RNA binding protein (RBP) human antigen R (HuR), and the intracellular localization of HuR responds to changes in mTORC1 activity. To expand these studies, we investigated whether HuR functions to regulate ODC mRNA stability after UVB exposure. Our results show an increased localization of HuR to the cytoplasm after UVB exposure in wild-type cells compared to Raptor knockout cells, and this is accompanied by greater association of HuR with the ODC transcript. These data suggest that the localization of HuR in response to UVB is influenced, at least in part, by mTORC1 and that HuR can bind to and stabilize ODC mRNA after UVB exposure in an mTORC1-dependent manner."
  • [DOI] A. Mai and S. L. Nowotarski, "Investigating ornithine decarboxylase posttranscriptional regulation via a pulldown assay using biotinylated transcripts," in Polyamines: methods and protocols, R. Alcázar and A. F. Tiburcio, Eds., New York, NY: Springer new york, 2018, p. 299–308.
    author="Mai, Anh
    and Nowotarski, Shannon L.",
    editor="Alc{\'a}zar, Rub{\'e}n
    and Tiburcio, Antonio F.",
    title="Investigating Ornithine Decarboxylase Posttranscriptional Regulation Via a Pulldown Assay Using Biotinylated Transcripts",
    bookTitle="Polyamines: Methods and Protocols",
    publisher="Springer New York",
    address="New York, NY",
    abstract="Ornithine decarboxylase (ODC) is the first rate-limiting enzyme in the polyamine biosynthetic pathway. It has been well documented that ODC is tightly regulated at the levels of transcription, posttranscriptional changes in RNA, and protein degradation during normal conditions and that these processes are dysregulated during tumorigenesis. Moreover, it has been recently shown that ODC is posttranscriptionally regulated by RNA binding proteins (RBPs) which can bind to the ODC mRNA transcript and alter its stability and translation. Using a mouse skin cancer model, we show that the RBP human antigen R (HuR) is able to bind to synthetic mRNA transcripts through a pulldown assay which utilizes a biotin-labeled ODC 3{\textasciiacutex}-untranslated region (UTR). The details of this method are described here. A better understanding of the mechanism(s) which regulates ODC is critical for targeting ODC in chemoprevention.",
  • [DOI] S. L. Nowotarski and L. M. Shantz, "The odc 3′-untranslated region and 5′-untranslated region contain cis-regulatory elements: implications for carcinogenesis," Medical sciences, vol. 6, iss. 1, 2018.
    AUTHOR = {Nowotarski, Shannon L. and Shantz, Lisa M.},
    TITLE = {The ODC 3′-Untranslated Region and 5′-Untranslated Region Contain cis-Regulatory Elements: Implications for Carcinogenesis},
    JOURNAL = {Medical Sciences},
    VOLUME = {6},
    YEAR = {2018},
    NUMBER = {1},
    URL = {https://www.mdpi.com/2076-3271/6/1/2},
    PubMedID = {29271923},
    ISSN = {2076-3271},
    ABSTRACT = {It has been hypothesized that both the 3′-untranslated region (3′UTR) and the 5′-untranslated region (5′UTR) of the ornithine decarboxylase (ODC) mRNA influence the expression of the ODC protein. Here, we use luciferase expression constructs to examine the influence of both UTRs in keratinocyte derived cell lines. The ODC 5′UTR or 3′UTR was cloned into the pGL3 control vector upstream or downstream of the luciferase reporter gene, respectively, and luciferase activity was measured in both non-tumorigenic and tumorigenic mouse keratinocyte cell lines. Further analysis of the influence of the 3′UTR on luciferase activity was accomplished through site-directed mutagenesis and distal deletion analysis within this region. Insertion of either the 5′UTR or 3′UTR into a luciferase vector resulted in a decrease in luciferase activity when compared to the control vector. Deletion analysis of the 3′UTR revealed a region between bases 1969 and 2141 that was inhibitory, and mutating residues within that region increased luciferase activity. These data suggest that both the 5′UTR and 3′UTR of ODC contain cis-acting regulatory elements that control intracellular ODC protein levels.},
    DOI = {10.3390/medsci6010002}


  • [DOI] A. Caro-Maldonado, L. Camacho, A. Zabala-Letona, V. Torrano, S. Fernández-Ruiz, K. Zamacola-Bascaran, L. Arreal, L. Valcárcel-Jiménez, N. Martín-Martín, J. M. Flores, A. R. Cortazar, P. Zúñiga-García, A. Arruabarrena-Aristorena, F. Guillaumond, D. Cabrera, J. M. Falcón-Perez, A. M. Aransay, A. Gomez-Muñoz, M. Olivan, J. Morote, and A. Carracedo, "Low-dose statin treatment increases prostate cancer aggressiveness," Oncotarget, vol. 9, iss. 2, pp. 1494-1504, 2017.
    @article{ OT22217,
    author = {Caro-Maldonado, Alfredo and Camacho, Laura and Zabala-Letona, Amaia and Torrano, Verónica and Fernández-Ruiz, Sonia and Zamacola-Bascaran, Kepa and Arreal, Leire and Valcárcel-Jiménez, Lorea and Martín-Martín, Natalia and Flores, Juana M and Cortazar, Ana R and Zúñiga-García, Patricia and Arruabarrena-Aristorena, Amaia and Guillaumond, Fabienne and Cabrera, Diana and Falcón-Perez, Juan M and Aransay, Ana M and Gomez-Muñoz, Antonio and Olivan, Mireia and Morote, Juan and Carracedo, Arkaitz},
    title = {Low-dose statin treatment increases prostate cancer aggressiveness},
    journal = {Oncotarget},
    volume = {9},
    number = {2},
    publisher = {Impact Journals, LLC},
    issn = {1949-2553},
    url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=22217},
    doi = {https://doi.org/10.18632/oncotarget.22217},
    pages = {1494-1504},
    year = {2017},
  • [DOI] B. Porteiro, M. F. Fondevila, T. C. Delgado, C. Iglesias, M. Imbernon, P. Iruzubieta, J. Crespo, A. Zabala-Letona, J. Fern{ø}, B. González-Terán, N. Matesanz, L. Hernández-Cosido, M. Marcos, S. Tovar, A. Vidal, J. Sánchez-Ceinos, M. M. Malagon, C. Pombo, J. Zalvide, A. Carracedo, X. Buque, C. Dieguez, G. Sabio, M. López, P. Aspichueta, M. L. Martínez-Chantar, and R. Nogueiras, "Hepatic p63 regulates steatosis via ikkb/er stress," Nature communications, vol. 8, iss. 1, p. 15111, 2017.
    author={Porteiro, Bego{\~n}a
    and Fondevila, Marcos F.
    and Delgado, Teresa C.
    and Iglesias, Cristina
    and Imbernon, Monica
    and Iruzubieta, Paula
    and Crespo, Javier
    and Zabala-Letona, Amaia
    and Fern{\o}, Johan
    and Gonz{\'a}lez-Ter{\'a}n, B{\'a}rbara
    and Matesanz, Nuria
    and Hern{\'a}ndez-Cosido, Lourdes
    and Marcos, Miguel
    and Tovar, Sulay
    and Vidal, Anxo
    and S{\'a}nchez-Ceinos, Julia
    and Malagon, Maria M.
    and Pombo, Celia
    and Zalvide, Juan
    and Carracedo, Arkaitz
    and Buque, Xabier
    and Dieguez, Carlos
    and Sabio, Guadalupe
    and L{\'o}pez, Miguel
    and Aspichueta, Patricia
    and Mart{\'i}nez-Chantar, Mar{\'i}a L.
    and Nogueiras, Ruben},
    title={Hepatic p63 regulates steatosis via IKKb/ER stress},
    journal={Nature Communications},
    abstract={p53 family members control several metabolic and cellular functions. The p53 ortholog p63 modulates cellular adaptations to stress and has a major role in cell maintenance and proliferation. Here we show that p63 regulates hepatic lipid metabolism. Mice with liver-specific p53 deletion develop steatosis and show increased levels of p63. Down-regulation of p63 attenuates liver steatosis in p53 knockout mice and in diet-induced obese mice, whereas the activation of p63 induces lipid accumulation. Hepatic overexpression of N-terminal transactivation domain TAp63 induces liver steatosis through IKKb activation and the induction of ER stress, the inhibition of which rescues the liver functions. Expression of TAp63, IKKb and XBP1s is also increased in livers of obese patients with NAFLD. In cultured human hepatocytes, TAp63 inhibition protects against oleic acid-induced lipid accumulation, whereas TAp63 overexpression promotes lipid storage, an effect reversible by IKKb silencing. Our findings indicate an unexpected role of the p63/IKKb/ER stress pathway in lipid metabolism and liver disease.},
  • [DOI] A. Zabala-Letona, A. Arruabarrena-Aristorena, N. Martín-Martín, S. Fernandez-Ruiz, J. D. Sutherland, M. Clasquin, J. Tomas-Cortazar, J. Jimenez, I. Torres, P. Quang, P. Ximenez-Embun, R. Bago, A. Ugalde-Olano, A. Loizaga-Iriarte, I. Lacasa-Viscasillas, M. Unda, V. Torrano, D. Cabrera, S. M. van Liempd, Y. Cendon, E. Castro, S. Murray, A. Revandkar, A. Alimonti, Y. Zhang, A. Barnett, G. Lein, D. Pirman, A. R. Cortazar, L. Arreal, L. Prudkin, I. Astobiza, L. Valcarcel-Jimenez, P. Zuñiga-García, I. Fernandez-Dominguez, M. Piva, A. Caro-Maldonado, P. Sánchez-Mosquera, M. Castillo-Martín, V. Serra, N. Beraza, A. Gentilella, G. Thomas, M. Azkargorta, F. Elortza, R. Farràs, D. Olmos, A. Efeyan, J. Anguita, J. Muñoz, J. M. Falcón-Pérez, R. Barrio, T. Macarulla, J. M. Mato, M. L. Martinez-Chantar, C. Cordon-Cardo, A. M. Aransay, K. Marks, J. Baselga, J. Tabernero, P. Nuciforo, B. D. Manning, K. Marjon, and A. Carracedo, "Mtorc1-dependent amd1 regulation sustains polyamine metabolism in prostate cancer," Nature, vol. 547, iss. 7661, pp. 109-113, 2017.
    author={Zabala-Letona, Amaia
    and Arruabarrena-Aristorena, Amaia
    and Mart{\'i}n-Mart{\'i}n, Natalia
    and Fernandez-Ruiz, Sonia
    and Sutherland, James D.
    and Clasquin, Michelle
    and Tomas-Cortazar, Julen
    and Jimenez, Jose
    and Torres, Ines
    and Quang, Phong
    and Ximenez-Embun, Pilar
    and Bago, Ruzica
    and Ugalde-Olano, Aitziber
    and Loizaga-Iriarte, Ana
    and Lacasa-Viscasillas, Isabel
    and Unda, Miguel
    and Torrano, Ver{\'o}nica
    and Cabrera, Diana
    and van Liempd, Sebastiaan M.
    and Cendon, Ylenia
    and Castro, Elena
    and Murray, Stuart
    and Revandkar, Ajinkya
    and Alimonti, Andrea
    and Zhang, Yinan
    and Barnett, Amelia
    and Lein, Gina
    and Pirman, David
    and Cortazar, Ana R.
    and Arreal, Leire
    and Prudkin, Ludmila
    and Astobiza, Ianire
    and Valcarcel-Jimenez, Lorea
    and Zu{\~n}iga-Garc{\'i}a, Patricia
    and Fernandez-Dominguez, Itziar
    and Piva, Marco
    and Caro-Maldonado, Alfredo
    and S{\'a}nchez-Mosquera, Pilar
    and Castillo-Mart{\'i}n, Mireia
    and Serra, Violeta
    and Beraza, Naiara
    and Gentilella, Antonio
    and Thomas, George
    and Azkargorta, Mikel
    and Elortza, Felix
    and Farr{\`a}s, Rosa
    and Olmos, David
    and Efeyan, Alejo
    and Anguita, Juan
    and Mu{\~n}oz, Javier
    and Falc{\'o}n-P{\'e}rez, Juan M.
    and Barrio, Rosa
    and Macarulla, Teresa
    and Mato, Jose M.
    and Martinez-Chantar, Maria L.
    and Cordon-Cardo, Carlos
    and Aransay, Ana M.
    and Marks, Kevin
    and Baselga, Jos{\'e}
    and Tabernero, Josep
    and Nuciforo, Paolo
    and Manning, Brendan D.
    and Marjon, Katya
    and Carracedo, Arkaitz},
    title={mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer},
    abstract={mTOR complex 1 signalling regulates polyamine metabolism and thereby promotes tumorigenesis, through regulation of the stability of a key enzyme, AMD1.},
  • [DOI] H. I. Kim, C. R. Schultz, A. L. Buras, E. Friedman, A. Fedorko, L. Seamon, G. V. R. Chandramouli, L. G. Maxwell, A. S. Bachmann, and J. I. Risinger, "Ornithine decarboxylase as a therapeutic target for endometrial cancer," Plos one, vol. 12, iss. 12, pp. 1-18, 2017.
    author = {Kim, Hong Im AND Schultz, Chad R. AND Buras, Andrea L. AND Friedman, Elizabeth AND Fedorko, Alyssa AND Seamon, Leigh AND Chandramouli, Gadisetti V. R. AND Maxwell, G. Larry AND Bachmann, André S. AND Risinger, John I.},
    journal = {PLOS ONE},
    publisher = {Public Library of Science},
    title = {Ornithine decarboxylase as a therapeutic target for endometrial cancer},
    year = {2017},
    month = {12},
    volume = {12},
    url = {https://doi.org/10.1371/journal.pone.0189044},
    pages = {1-18},
    abstract = {Ornithine Decarboxylase (ODC) a key enzyme in polyamine biosynthesis is often overexpressed in cancers and contributes to polyamine-induced cell proliferation. We noted ubiquitous expression of ODC1 in our published endometrial cancer gene array data and confirmed this in the cancer genome atlas (TCGA) with highest expression in non-endometrioid, high grade, and copy number high cancers, which have the worst clinical outcomes. ODC1 expression was associated with worse overall survival and increased recurrence in three endometrial cancer gene expression datasets. Importantly, we confirmed these findings using quantitative real-time polymerase chain reaction (qRT-PCR) in a validation cohort of 60 endometrial cancers and found that endometrial cancers with elevated ODC1 had significantly shorter recurrence-free intervals (KM log-rank p = 0.0312, Wald test p = 5.59e-05). Difluoromethylornithine (DFMO) a specific inhibitor of ODC significantly reduced cell proliferation, cell viability, and colony formation in cell line models derived from undifferentiated, endometrioid, serous, carcinosarcoma (mixed mesodermal tumor; MMT) and clear cell endometrial cancers. DFMO also significantly reduced human endometrial cancer ACI-98 tumor burden in mice compared to controls (p = 0.0023). ODC-regulated polyamines (putrescine [Put] and/or spermidine [Spd]) known activators of cell proliferation were strongly decreased in response to DFMO, in both tumor tissue ([Put] (p = 0.0006), [Spd] (p<0.0001)) and blood plasma ([Put] (p<0.0001), [Spd] (p = 0.0049)) of treated mice. Our study indicates that some endometrial cancers appear particularly sensitive to DFMO and that the polyamine pathway in endometrial cancers in general and specifically those most likely to suffer adverse clinical outcomes could be targeted for effective treatment, chemoprevention or chemoprevention of recurrence.},
    number = {12},
    doi = {10.1371/journal.pone.0189044}
  • F. W. Bazer and W. W. Thatcher, "Chronicling the discovery of interferon tau," Reproduction, vol. 154, iss. 5", pages: "F11 - F20, 2017.
    @article { Chroniclingthediscoveryofinterferontau,
    author = "Fuller W Bazer and William W Thatcher",
    title = "Chronicling the discovery of interferon tau",
    journal = "Reproduction",
    year = "2017",
    publisher = "Bioscientifica Ltd",
    address = "Bristol, UK",
    volume = "154",
    number = "5",
    pages: "F11 - F20",
    url = "https://rep.bioscientifica.com/view/journals/rep/154/5/REP-17-0257.xml"


  • [DOI] N. Martín-Martín, M. Piva, J. Urosevic, P. Aldaz, J. D. Sutherland, S. Fernández-Ruiz, L. Arreal, V. Torrano, A. R. Cortazar, E. Planet, M. Guiu, N. Radosevic-Robin, S. Garcia, I. Macías, F. Salvador, G. Domenici, O. M. Rueda, A. Zabala-Letona, A. Arruabarrena-Aristorena, P. Zúñiga-García, A. Caro-Maldonado, L. Valcárcel-Jiménez, P. Sánchez-Mosquera, M. Varela-Rey, M. L. Martínez-Chantar, J. Anguita, Y. H. Ibrahim, M. Scaltriti, C. H. Lawrie, A. M. Aransay, J. L. Iovanna, J. Baselga, C. Caldas, R. Barrio, V. Serra, M. dM Vivanco, A. Matheu, R. R. Gomis, and A. Carracedo, "Stratification and therapeutic potential of pml in metastatic breast cancer," Nature communications, vol. 7, iss. 1, p. 12595, 2016.
    author={Mart{\'i}n-Mart{\'i}n, Natalia
    and Piva, Marco
    and Urosevic, Jelena
    and Aldaz, Paula
    and Sutherland, James D.
    and Fern{\'a}ndez-Ruiz, Sonia
    and Arreal, Leire
    and Torrano, Ver{\'o}nica
    and Cortazar, Ana R.
    and Planet, Evarist
    and Guiu, Marc
    and Radosevic-Robin, Nina
    and Garcia, Stephane
    and Mac{\'i}as, Iratxe
    and Salvador, Fernando
    and Domenici, Giacomo
    and Rueda, Oscar M.
    and Zabala-Letona, Amaia
    and Arruabarrena-Aristorena, Amaia
    and Z{\'u}{\~n}iga-Garc{\'i}a, Patricia
    and Caro-Maldonado, Alfredo
    and Valc{\'a}rcel-Jim{\'e}nez, Lorea
    and S{\'a}nchez-Mosquera, Pilar
    and Varela-Rey, Marta
    and Mart{\'i}nez-Chantar, Maria Luz
    and Anguita, Juan
    and Ibrahim, Yasir H.
    and Scaltriti, Maurizio
    and Lawrie, Charles H.
    and Aransay, Ana M.
    and Iovanna, Juan L.
    and Baselga, Jose
    and Caldas, Carlos
    and Barrio, Rosa
    and Serra, Violeta
    and dM Vivanco, Maria
    and Matheu, Ander
    and Gomis, Roger R.
    and Carracedo, Arkaitz},
    title={Stratification and therapeutic potential of PML in metastatic breast cancer},
    journal={Nature Communications},
    abstract={Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification.},
  • [DOI] V. Torrano, L. Valcarcel-Jimenez, A. R. Cortazar, X. Liu, J. Urosevic, M. Castillo-Martin, S. Fernández-Ruiz, G. Morciano, A. Caro-Maldonado, M. Guiu, P. Zúñiga-García, M. Graupera, A. Bellmunt, P. Pandya, M. Lorente, N. Martín-Martín, J. D. Sutherland, P. Sanchez-Mosquera, L. Bozal-Basterra, A. Zabala-Letona, A. Arruabarrena-Aristorena, A. Berenguer, N. Embade, A. Ugalde-Olano, I. Lacasa-Viscasillas, A. Loizaga-Iriarte, M. Unda-Urzaiz, N. Schultz, A. M. Aransay, V. Sanz-Moreno, R. Barrio, G. Velasco, P. Pinton, C. Cordon-Cardo, J. W. Locasale, R. R. Gomis, and A. Carracedo, "The metabolic co-regulator pgc1a suppresses prostate cancer metastasis," Nature cell biology, vol. 18, iss. 6, pp. 645-656, 2016.
    author={Torrano, Veronica
    and Valcarcel-Jimenez, Lorea
    and Cortazar, Ana Rosa
    and Liu, Xiaojing
    and Urosevic, Jelena
    and Castillo-Martin, Mireia
    and Fern{\'a}ndez-Ruiz, Sonia
    and Morciano, Giampaolo
    and Caro-Maldonado, Alfredo
    and Guiu, Marc
    and Z{\'u}{\~n}iga-Garc{\'i}a, Patricia
    and Graupera, Mariona
    and Bellmunt, Anna
    and Pandya, Pahini
    and Lorente, Mar
    and Mart{\'i}n-Mart{\'i}n, Natalia
    and Sutherland, James David
    and Sanchez-Mosquera, Pilar
    and Bozal-Basterra, Laura
    and Zabala-Letona, Amaia
    and Arruabarrena-Aristorena, Amaia
    and Berenguer, Antonio
    and Embade, Nieves
    and Ugalde-Olano, Aitziber
    and Lacasa-Viscasillas, Isabel
    and Loizaga-Iriarte, Ana
    and Unda-Urzaiz, Miguel
    and Schultz, Nikolaus
    and Aransay, Ana Maria
    and Sanz-Moreno, Victoria
    and Barrio, Rosa
    and Velasco, Guillermo
    and Pinton, Paolo
    and Cordon-Cardo, Carlos
    and Locasale, Jason W.
    and Gomis, Roger R.
    and Carracedo, Arkaitz},
    title={The metabolic co-regulator PGC1a suppresses prostate cancer metastasis},
    journal={Nature Cell Biology},
    abstract={Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1a (PGC1a) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1a is downregulated in prostate cancer and associated with disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1a opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1a activates an oestrogen-related receptor alpha (ERRa)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1a-ERRa pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment.},
  • [DOI] F. Royo, P. Zuñiga-Garcia, V. Torrano, A. Loizaga, P. Sanchez-Mosquera, A. Ugalde-Olano, E. González, A. R. Cortazar, L. Palomo, S. Fernández-Ruiz, I. Lacasa-Viscasillas, M. Berdasco, J. D. Sutherland, R. Barrio, A. Zabala-Letona, N. Martín-Martín, A. Arruabarrena-Aristorena, L. Valcarcel-Jimenez, A. Caro-Maldonado, J. Gonzalez-Tampan, G. Cachi-Fuentes, M. Esteller, A. M. Aransay, M. Unda, J. M. Falcón-Pérez, and A. Carracedo, "Transcriptomic profiling of urine extracellular vesicles reveals alterations of cdh3 in prostate cancer," Oncotarget, vol. 7, iss. 6, pp. 6835-6846, 2016.
    @article{ OT6899,
    author = {Royo, Felix and Zuñiga-Garcia, Patricia and Torrano, Verónica and Loizaga, Ana and Sanchez-Mosquera, Pilar and Ugalde-Olano, Aitziber and González, Esperanza and Cortazar, Ana R and Palomo, Laura and Fernández-Ruiz, Sonia and Lacasa-Viscasillas, Isabel and Berdasco, Maria and Sutherland, James D and Barrio, Rosa and Zabala-Letona, Amaia and Martín-Martín, Natalia and Arruabarrena-Aristorena, Amaia and Valcarcel-Jimenez, Lorea and Caro-Maldonado, Alfredo and Gonzalez-Tampan, Jorge and Cachi-Fuentes, Guido and Esteller, Manel and Aransay, Ana M and Unda, Miguel and Falcón-Pérez, Juan M and Carracedo, Arkaitz},
    title = {Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer},
    journal = {Oncotarget},
    volume = {7},
    number = {6},
    publisher = {Impact Journals, LLC},
    issn = {1949-2553},
    url = {http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=6899},
    doi = {https://doi.org/10.18632/oncotarget.6899},
    pages = {6835-6846},
    year = {2016},
  • [DOI] C. S. Filgueira, E. Nicolov, R. L. Hood, A. Ballerini, J. Garcia-Huidobro, J. Z. Lin, D. Fraga, P. Webb, O. M. Sabek, A. O. Gaber, K. J. Phillips, and A. Grattoni, "Sustained zero-order delivery of gc-1 from a nanochannel membrane device alleviates metabolic syndrome," International journal of obesity, vol. 40, iss. 11, pp. 1776-1783, 2016.
    author={Filgueira, C. S.
    and Nicolov, E.
    and Hood, R. L.
    and Ballerini, A.
    and Garcia-Huidobro, J.
    and Lin, J. Z.
    and Fraga, D.
    and Webb, P.
    and Sabek, O. M.
    and Gaber, A. O.
    and Phillips, K. J.
    and Grattoni, A.},
    title={Sustained zero-order delivery of GC-1 from a nanochannel membrane device alleviates metabolic syndrome},
    journal={International Journal of Obesity},
    abstract={Our objective was to assess the sustained, low-dose and constant administration of the thyroid receptor-b (TRb)-selective agonist GC-1 (sobetirome) from a novel nanochannel membrane device (NMD) for drug delivery. As it known to speed up metabolism, accomplish weight loss, improve cholesterol levels and possess anti-diabetic effects, GC-1 was steadily administered by our NMD, consisting of an implantable nanochannel membrane, as an alternative to conventional daily administration, which is subject to compliance issues in clinical settings.},
  • [DOI] S. L. Nowotarski, S. Origanti, S. Sass-Kuhn, and L. M. Shantz, "Destabilization of the ornithine decarboxylase mrna transcript by the rna-binding protein tristetraprolin," Amino acids, vol. 48, iss. 10, p. 2303–2311, 2016.
    author="Nowotarski, Shannon L.
    and Origanti, Sofia
    and Sass-Kuhn, Suzanne
    and Shantz, Lisa M.",
    title="Destabilization of the ornithine decarboxylase mRNA transcript by the RNA-binding protein tristetraprolin",
    journal="Amino Acids",
    abstract="Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3{\textasciiacutex} untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript.",


  • [DOI] N. Paz, I. Felipe-Blanco, F. Royo, A. Zabala, I. Guerra-Merino, Á. García-Orad, J. L. Zugaza, and L. A. Parada, "Expression of the dyrk1a gene correlates with its 3d positioning in the interphase nucleus of down syndrome cells," Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology, vol. 23, iss. 2, pp. 285-298, 2015.
    author={Paz, Nerea
    and Felipe-Blanco, Izaskun
    and Royo, F{\'e}lix
    and Zabala, Amaia
    and Guerra-Merino, Isabel
    and Garc{\'i}a-Orad, {\'A}frica
    and Zugaza, Jos{\'e} L.
    and Parada, Luis A.},
    title={Expression of the DYRK1A gene correlates with its 3D positioning in the interphase nucleus of Down syndrome cells},
    journal={Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology},
    keywords={Gene Expression},
  • [DOI] A. Ugalde-Olano, A. Egia, S. Fernández-Ruiz, A. Loizaga-Iriarte, P. Zuñiga-García, S. Garcia, F. Royo, I. Lacasa-Viscasillas, E. Castro, A. R. Cortazar, A. Zabala-Letona, N. Martín-Martín, A. Arruabarrena-Aristorena, V. Torrano-Moya, L. Valcárcel-Jiménez, P. Sánchez-Mosquera, A. Caro-Maldonado, J. González-Tampan, G. Cachi-Fuentes, E. Bilbao, R. Montero, S. Fernández, E. Arrieta, K. Zorroza, M. Castillo-Martín, V. Serra, E. Salazar, N. Macías-Cámara, J. Tabernero, J. Baselga, C. Cordón-Cardo, A. M. Aransay, A. D. Villar, J. L. Iovanna, J. M. Falcón-Pérez, M. Unda, R. Bilbao, and A. Carracedo, "Methodological aspects of the molecular and histological study of prostate cancer: focus on pten," Methods, vol. 77-78, pp. 25-30, 2015.
    title = "Methodological aspects of the molecular and histological study of prostate cancer: Focus on PTEN",
    journal = "Methods",
    volume = "77-78",
    pages = "25 - 30",
    year = "2015",
    note = "PTEN Function Methods",
    issn = "1046-2023",
    doi = "https://doi.org/10.1016/j.ymeth.2015.02.005",
    url = "http://www.sciencedirect.com/science/article/pii/S1046202315000456",
    author = "Aitziber Ugalde-Olano and Ainara Egia and Sonia Fernández-Ruiz and Ana Loizaga-Iriarte and Patricia Zuñiga-García and Stephane Garcia and Félix Royo and Isabel Lacasa-Viscasillas and Erika Castro and Ana R. Cortazar and Amaia Zabala-Letona and Natalia Martín-Martín and Amaia Arruabarrena-Aristorena and Verónica Torrano-Moya and Lorea Valcárcel-Jiménez and Pilar Sánchez-Mosquera and Alfredo Caro-Maldonado and Jorge González-Tampan and Guido Cachi-Fuentes and Elena Bilbao and Rocío Montero and Sara Fernández and Edurne Arrieta and Kerman Zorroza and Mireia Castillo-Martín and Violeta Serra and Eider Salazar and Nuria Macías-Cámara and Jose Tabernero and Jose Baselga and Carlos Cordón-Cardo and Ana M. Aransay and Amaia Del Villar and Juan L. Iovanna and Juan M. Falcón-Pérez and Miguel Unda and Roberto Bilbao and Arkaitz Carracedo",
    keywords = "PTEN, Prostate cancer, Fresh tissue, Molecular biology",
    abstract = "Prostate cancer is among the most frequent cancers in men, and despite its high rate of cure, the high number of cases results in an elevated mortality worldwide. Importantly, prostate cancer incidence is dramatically increasing in western societies in the past decades, suggesting that this type of tumor is exquisitely sensitive to lifestyle changes. Prostate cancer frequently exhibits alterations in the PTEN gene (inactivating mutations or gene deletions) or at the protein level (reduced protein expression or altered sub-cellular compartmentalization). The relevance of PTEN in this type of cancer is further supported by the fact that the sole deletion of PTEN in the murine prostate epithelium recapitulates many of the features of the human disease. In order to study the molecular alterations in prostate cancer, we need to overcome the methodological challenges that this tissue imposes. In this review we present protocols and methods, using PTEN as proof of concept, to study different molecular characteristics of prostate cancer."
  • [DOI] F. Bazer, "History of maternal recognition of pregnancy," Advances in anatomy embryology and cell biology, vol. 216, pp. 5-25, 2015.
    author = {Bazer, Fuller},
    year = {2015},
    month = {01},
    pages = {5-25},
    title = {History of Maternal Recognition of Pregnancy},
    volume = {216},
    journal = {Advances in Anatomy Embryology and Cell Biology},
    doi = {10.1007/978-3-319-15856-3_2}


  • [DOI] N. Paz, A. Zabala, F. Royo, Á. García-Orad, J. L. Zugaza, and L. A. Parada, "Combined fluorescent-chromogenic in situ hybridization for identification and laser microdissection of interphase chromosomes," Plos one, vol. 8, iss. 4, pp. 1-9, 2013.
    author = {Paz, Nerea AND Zabala, Amaia AND Royo, Félix AND García-Orad, África AND Zugaza, José L. AND Parada, Luis A.},
    journal = {PLOS ONE},
    publisher = {Public Library of Science},
    title = {Combined Fluorescent-Chromogenic In Situ Hybridization for Identification and Laser Microdissection of Interphase Chromosomes},
    year = {2013},
    month = {04},
    volume = {8},
    url = {https://doi.org/10.1371/journal.pone.0060238},
    pages = {1-9},
    abstract = {Chromosome territories constitute the most conspicuous feature of nuclear architecture, and they exhibit non-random distribution patterns in the interphase nucleus. We observed that in cell nuclei from humans with Down Syndrome two chromosomes 21 frequently localize proximal to one another and distant from the third chromosome. To systematically investigate whether the proximally positioned chromosomes were always the same in all cells, we developed an approach consisting of sequential FISH and CISH combined with laser-microdissection of chromosomes from the interphase nucleus and followed by subsequent chromosome identification by microsatellite allele genotyping. This approach identified proximally positioned chromosomes from cultured cells, and the analysis showed that the identity of the chromosomes proximally positioned varies. However, the data suggest that there may be a tendency of the same chromosomes to be positioned close to each other in the interphase nucleus of trisomic cells. The protocol described here represents a powerful new method for genome analysis.},
    number = {4},
    doi = {10.1371/journal.pone.0060238}


  • [DOI] A. Z. Letona, I. Niot, F. Laugerette, A. Athias, M. Monnot, M. P. Portillo, P. Besnard, and H. Poirier, "CLA-Enriched Diet Containing t10,c12-CLA Alters Bile Acid Homeostasis and Increases the Risk of Cholelithiasis in Mice," The journal of nutrition, vol. 141, iss. 8, pp. 1437-1444, 2011.
    author = {Letona, Amaia Zabala and Niot, Isabelle and Laugerette, Fabienne and Athias, Anne and Monnot, Marie-Claude and Portillo, Maria P. and Besnard, Philippe and Poirier, Hélène},
    title = "{CLA-Enriched Diet Containing t10,c12-CLA Alters Bile Acid Homeostasis and Increases the Risk of Cholelithiasis in Mice}",
    journal = {The Journal of Nutrition},
    volume = {141},
    number = {8},
    pages = {1437-1444},
    year = {2011},
    month = {05},
    abstract = "{Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the entero-hepatic circulation of BA was altered due to greater BA synthesis and ileal reclamation. This resulted from higher hepatic cholesterol 7α-hydroxylase (CYP7A1) and ileal apical sodium BA transporter expressions in CLA-fed mice. Furthermore, hepatic Na+/taurocholate co-transporting polypeptide (NTCP) (−52\\%) and bile salt export pump (BSEP) (−77\\%) protein levels were lower in CLA-fed mice than in controls, leading to a greater accumulation of BA in the plasma (+500\\%); also, the cholesterol saturation index and the concentration of hydrophobic BA in the bile were greater in CLA-fed mice, changes associated with the presence of cholesterol crystals. Expt. 2 suggests that CLA-mediated changes were caused by hyperinsulinemia, which occurred after 6 d of the CLA diet before NTCP and BSEP mRNA downregulation (10 d). Expt. 3 demonstrated that only t10,c12-CLA altered NTCP and BSEP mRNA levels. In conclusion, t10,c12-CLA alters BA homeostasis and increases the risk of cholelithiasis in mice.}",
    issn = {0022-3166},
    doi = {10.3945/jn.110.136168},
    url = {https://doi.org/10.3945/jn.110.136168},
    eprint = {http://oup.prod.sis.lan/jn/article-pdf/141/8/1437/23948832/1437.pdf},
  • [DOI] F. W. Bazer, "Contributions of an Animal Scientist to Reproductive Biology," Biology of reproduction, vol. 85, iss. 2, pp. 228-242, 2011.
    author = {Bazer, Fuller W.},
    title = "{Contributions of an Animal Scientist to Reproductive Biology}",
    journal = {Biology of Reproduction},
    volume = {85},
    number = {2},
    pages = {228-242},
    year = {2011},
    month = {08},
    abstract = "{I became interested in biology as an undergraduate in a premedical curriculum but developed a passion for the field of reproductive biology because of a course in physiology of reproduction taken to meet requirements for admission to veterinary school. My career path changed, and I entered graduate school, obtained the Ph.D., and have enjoyed an academic career as a reproductive biologist conducting research in uterine biology and pregnancy in animal science departments at the University of Florida and at Texas A\\&M University. However, I have never allowed academic boundaries to interfere with research and graduate education as that is contrary to collegiality, the cornerstone of great universities. I consider that my major contributions to science include 1) identification of proteins secreted by cells of the uterine endometrium that are critical to successful establishment and maintenance of pregnancy; 2) discovery of steroids and proteins required for pregnancy recognition signaling and their mechanisms of action in pigs and ruminant species; 3) investigation of fetal-placental development and placental transport of nutrients, including water and electrolytes; 4) identification of linkages between nutrition and fetal-placental development; 5) defining aspects of the endocrinology of pregnancy; and 6) contributing to efforts to exploit the therapeutic value of interferon tau, particularly for treatment of autoimmune diseases. My current studies are focused on the role of select nutrients in the uterine lumen, specifically amino acids and glucose, that affect development and survival of the conceptus and translation of mRNAs and, with colleagues at Seoul National University, gene expression by the avian reproductive tract at key periods postovulation. Another goal is to understand stromal-epithelial cell signaling, whereby progesterone and estrogen act via uterine stromal cells that express receptors for sex steroids to stimulate secretion of growth factors (e.g., fibroblast growth factors and hepatocyte growth factor) that, in turn, regulate functions of uterine epithelial cells and conceptus trophectoderm.}",
    issn = {0006-3363},
    doi = {10.1095/biolreprod.111.091454},
    url = {https://doi.org/10.1095/biolreprod.111.091454},
    eprint = {http://oup.prod.sis.lan/biolreprod/article-pdf/85/2/228/10575946/biolreprod0228.pdf},


  • [DOI] A. Letona, M. Portillo, V. Navarro, M. Macarulla, L. Barron, and A. Fernández-Quintela, "Quantitative gas chromatographic method for the analysis of cis-9, trans-11 and trans-10, cis-12 isomers of the conjugated linoleic acid in liver," Journal of chromatography. b, analytical technologies in the biomedical and life sciences, vol. 855, pp. 152-8, 2007.
    author = {Letona, Amaia and Portillo, María and Navarro, Virginia and Macarulla, María and Barron, Luis and Fernández-Quintela, Alfredo},
    year = {2007},
    month = {09},
    pages = {152-8},
    title = {Quantitative gas chromatographic method for the analysis of cis-9, trans-11 and trans-10, cis-12 isomers of the conjugated linoleic acid in liver},
    volume = {855},
    journal = {Journal of chromatography. B, Analytical technologies in the biomedical and life sciences},
    doi = {10.1016/j.jchromb.2007.04.041}


  • [DOI] A. Zabala, I. Churruca, A. Fernández-Quintela, V. M. Rodríguez, T. M. Macarulla, A. J. Martínez, and M. P. Portillo, "Trans-10, cis-12 conjugated linoleic acid inhibits lipoprotein lipase but increases the activity of lipogenic enzymes in adipose tissue from hamsters fed an atherogenic diet," British journal of nutrition, vol. 95, iss. 6, p. 1112–1119, 2006.
    @article{zabala_churruca_fernández-quintela_rodríguez_macarulla_martínez_portillo_2006, title={trans-10, cis-12 Conjugated linoleic acid inhibits lipoprotein lipase but increases the activity of lipogenic enzymes in adipose tissue from hamsters fed an atherogenic diet}, volume={95}, DOI={10.1079/BJN20061774}, number={6}, journal={British Journal of Nutrition}, publisher={Cambridge University Press}, author={Zabala, Amaia and Churruca, Itziar and Fernández-Quintela, Alfredo and Rodríguez, Víctor M. and Macarulla, M. Teresa and Martínez, J. Alfredo and Portillo, María P.}, year={2006}, pages={1112–1119}}
  • [DOI] A. Zabala, M. P. Portillo, M. T. Macarulla, V. M. Rodríguez, and A. Fernández-Quintela, "Effects of cis-9, trans-11 and trans-10, cis-12 cla isomers on liver and adipose tissue fatty acid profile in hamsters," Lipids, vol. 41, iss. 11, p. 993–1001, 2006.
    author="Zabala, A.
    and Portillo, M. P.
    and Macarulla, M. T.
    and Rodr{\'i}guez, V. M.
    and Fern{\'a}ndez-Quintela, A.",
    title="Effects of cis-9, trans-11 and trans-10, cis-12 CLA isomers on liver and adipose tissue fatty acid profile in hamsters",
    abstract="The aim of the present study was to investigate the effect of cis-9, trans-11 and trans-10, cis-12 CLA on FA composition of TAG in epididymal adipose tissue and liver, and of hepatic phospholipids PL. Twenty-four Syrian Golden hamsters were randomly divided into three groups of eight animals each and fed semipurified atherogenic diets supplemented with either 0.5 g/100g diet of linoleic acid or cis-9, trans-11 or trans-12, cis-9 CLA for 6 wk. Total lipids were extracted, and TAG and PL were separated by TLC. FA profile in lipid species from liver and adipose tissue, as well as in feces, was determined by GC. Trans-10, cis-12 CLA feeding significantly reduced linoleic and linolenic acids in TAG from both tissues, leading to reduced total PUFA content. Moreover, in the epididymal adipose tissue docosenoic and arachidonic acids were significantly increased. In liver PL, although no changes in individual FA were observed, total saturated FA (SFA) were decreased. No changes in TAG and PL FA profiles were induced by the cis-9, trans-11 CLA. TAG and PL incorporated cis-9, trans-11 more readily than trans-11, cis-12 CLA. This difference was not due to differential intestinal absorption, as shown by the analysis of feces. We concluded that only trans-10, cis-12 CLA induces changes in FA composition. Whereas increased PUFA content was observed in either liver or adipose tissue TAG, decreased SFA were found in liver PL. Incorporation of cis-9, trans-11 CLA in TAG is greater than that of trans-10, cis-12 CLA, but this is not due to differences in intestinal absorption.",
  • [DOI] A. Zabala, A. Fernández-Quintela, T. M. Macarulla, E. Simón, V. M. Rodríguez, V. Navarro, and M. P. Portillo, "Effects of conjugated linoleic acid on skeletal muscle triacylglycerol metabolism in hamsters," Nutrition, vol. 22, iss. 5, pp. 528-533, 2006.
    title = "Effects of conjugated linoleic acid on skeletal muscle triacylglycerol metabolism in hamsters",
    journal = "Nutrition",
    volume = "22",
    number = "5",
    pages = "528 - 533",
    year = "2006",
    issn = "0899-9007",
    doi = "https://doi.org/10.1016/j.nut.2005.10.005",
    url = "http://www.sciencedirect.com/science/article/pii/S0899900705003497",
    author = "Amaia Zabala and Alfredo Fernández-Quintela and M. Teresa Macarulla and Edurne Simón and Víctor M. Rodríguez and Virginia Navarro and María P. Portillo",
    keywords = "Conjugated linoleic acid, Muscle composition, Lipoprotein lipase, Carnitine palmitoyltransferase-I, Hamster",
    abstract = "Objective
    The present work evaluated the effects of conjugated linoleic acid (CLA) on various aspects of triacylglycerol metabolism in skeletal muscle to determine the potential involvement of this tissue in the effect of CLA to decrease body fat.
    Animals were randomized to three groups that were fed atherogenic diets that provided different amounts of trans-10,cis-12 CLA (0%, 0.5%, or 1%) for 6 wk. Muscle triacylglycerol, protein, water, glycogen, and DNA contents and fatty acid profile in triacylglycerols were analyzed. Lipoprotein lipase and carnitine palmitoyltransferase-I (CPT-I) activities were assessed. Triacylglycerol, glucose, and insulin concentrations were evaluated in serum.
    The high dose of CLA increased food efficiency and gastrocnemius muscle weight. CLA feeding resulted in decreased muscle triacylglycerol content without changes in protein, water, glycogen, and DNA contents or in cell size (protein/DNA ratio) and produced decreased lipoprotein lipase activity and increased CPT-I activity. No differences were found between CLA doses. CLA feeding led to the saturation of stored triacylglycerols.
    Decreased fatty acid uptake and increased fatty acid oxidation can contribute to the decreased muscle triacylglycerol content observed in hamsters fed the CLA diets. The increase in muscle fatty acid β-oxidation might ultimately prevent storage of triacylglycerols in adipose tissue. Nevertheless, the lack of matching of lipoprotein lipase and CPT-I modifications makes it difficult to ensure that skeletal muscle is responsible, at least in part, for the effect of CLA on decreasing body fat; thus, further research is needed."


  • [DOI] M. Macarulla, A. Fernández-Quintela, A. Letona, V. Navarro, E. Echevarria, I. Churruca, V. M. Rodriguez, and M. Portillo, "Effects of conjugated linoleic acid on liver composition and fatty aid oxidation are isomer-dependent in hamster," Nutrition (burbank, los angeles county, calif.), vol. 21, pp. 512-9, 2005.
    author = {Macarulla, María and Fernández-Quintela, Alfredo and Letona, Amaia and Navarro, Virginia and Echevarria, Elizabeth and Churruca, Itziar and Rodriguez, Victor Manuel and Portillo, María},
    year = {2005},
    month = {05},
    pages = {512-9},
    title = {Effects of conjugated linoleic acid on liver composition and fatty aid oxidation are isomer-dependent in hamster},
    volume = {21},
    journal = {Nutrition (Burbank, Los Angeles County, Calif.)},
    doi = {10.1016/j.nut.2004.07.011}


  • [DOI] A. Zabala, I. Churruca, T. M. Macarulla, V. M. Rodríguez, A. Fernández-Quintela, A. J. Martínez, and M. P. Portillo, "The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic triacylglycerol content without affecting lipogenic enzymes in hamsters," British journal of nutrition, vol. 92, iss. 3, p. 383–389, 2004.
    @article{zabala_churruca_macarulla_rodríguez_fernández-quintela_martínez_portillo_2004, title={The trans-10,cis-12 isomer of conjugated linoleic acid reduces hepatic triacylglycerol content without affecting lipogenic enzymes in hamsters}, volume={92}, DOI={10.1079/BJN20041220}, number={3}, journal={British Journal of Nutrition}, publisher={Cambridge University Press}, author={Zabala, Amaia and Churruca, Itziar and Macarulla, M. Teresa and Rodríguez, Víctor M. and Fernández-Quintela, Alfredo and Martínez, J. Alfredo and Portillo, María P.}, year={2004}, pages={383–389}}


  • [DOI] V. Navarro, A. Letona, M. Macarulla, A. Fernández-Quintela, V. M. Rodriguez, E. Simón, and M. Portillo, "Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet," Journal of physiology and biochemistry, vol. 59, pp. 193-9, 2003.
    author = {Navarro, Virginia and Letona, Amaia and Macarulla, María and Fernández-Quintela, Alfredo and Rodriguez, Victor Manuel and Simón, Edurne and Portillo, María},
    year = {2003},
    month = {10},
    pages = {193-9},
    title = {Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet},
    volume = {59},
    journal = {Journal of physiology and biochemistry},
    doi = {10.1007/BF03179915}