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  1. Article ; Online: SPHINX-Based Combination Therapy as a Potential Novel Treatment Strategy for Acute Myeloid Leukaemia.

    Wodi, Chigeru / Belali, Tareg / Morse, Ruth / Porazinski, Sean / Ladomery, Michael

    British journal of biomedical science

    2023  Volume 80, Page(s) 11041

    Abstract: Introduction: ...

    Abstract Introduction:
    MeSH term(s) Humans ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/genetics ; Azacitidine/pharmacology ; Azacitidine/therapeutic use ; Drug Resistance, Neoplasm/genetics ; Imatinib Mesylate/pharmacology ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Protein Serine-Threonine Kinases/pharmacology ; Protein Serine-Threonine Kinases/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols
    Chemical Substances Antineoplastic Agents ; Azacitidine (M801H13NRU) ; Imatinib Mesylate (8A1O1M485B) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; SRPK1 protein, human (EC 2.7.1.-)
    Language English
    Publishing date 2023-02-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1152119-3
    ISSN 2474-0896 ; 0967-4845
    ISSN (online) 2474-0896
    ISSN 0967-4845
    DOI 10.3389/bjbs.2023.11041
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  2. Article ; Online: Working with Hypoxia.

    Bowler, Elizabeth / Ladomery, Michael R

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 1990, Page(s) 109–133

    Abstract: A hypoxic environment can be defined as a region of the body or the whole body that is deprived of oxygen. Hypoxia is a feature of many diseases, such as cardiovascular disease, tissue trauma, stroke, and solid cancers. A loss of oxygen supply usually ... ...

    Abstract A hypoxic environment can be defined as a region of the body or the whole body that is deprived of oxygen. Hypoxia is a feature of many diseases, such as cardiovascular disease, tissue trauma, stroke, and solid cancers. A loss of oxygen supply usually results in cell death; however, when cells gradually become hypoxic, they may survive and continue to thrive as described for conditions that promote metastatic growth. The role of hypoxia in these pathogenic pathways is therefore of great interest, and understanding the effect of hypoxia in regulating these mechanisms is fundamentally important. This chapter gives an extensive overview of these mechanisms. Moreover, given the challenges posed by tumor hypoxia we describe the current methods to simulate and detect hypoxic conditions followed by a discussion on current and experimental therapies that target hypoxic cells.
    MeSH term(s) Biomarkers, Tumor/metabolism ; Humans ; Hypoxia/physiopathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Oxygen/analysis ; Oxygen/metabolism ; Reactive Oxygen Species/metabolism
    Chemical Substances Biomarkers, Tumor ; Hypoxia-Inducible Factor 1, alpha Subunit ; Reactive Oxygen Species ; Oxygen (S88TT14065)
    Language English
    Publishing date 2019-05-16
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9463-2_10
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  3. Article ; Online: Going circular: history, present, and future of circRNAs in cancer.

    Pisignano, Giuseppina / Michael, David C / Visal, Tanvi H / Pirlog, Radu / Ladomery, Michael / Calin, George A

    Oncogene

    2023  Volume 42, Issue 38, Page(s) 2783–2800

    Abstract: To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and ... ...

    Abstract To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their circular shape limits their annotation and a complete functional elucidation is lacking. This makes their detection and biomedical application still challenging. Herein, we review the current knowledge of circRNA biogenesis and function, and of their involvement in tumorigenesis and potential utility in cancer-targeted therapy.
    MeSH term(s) Humans ; RNA, Circular/genetics ; Neoplasms/genetics ; Carcinogenesis ; RNA/genetics ; Cell Transformation, Neoplastic
    Chemical Substances RNA, Circular ; RNA (63231-63-0)
    Language English
    Publishing date 2023-08-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-023-02780-w
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    Zs.A 2218: Show issues Location:
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  4. Article ; Online: Role of splice variants in the metastatic progression of prostate cancer.

    Hagen, Rachel M / Ladomery, Michael R

    Biochemical Society transactions

    2012  Volume 40, Issue 4, Page(s) 870–874

    Abstract: AS (alternative splicing) and its role in disease, especially cancer, has come to forefront in research over the last few years. Alterations in the ratio of splice variants have been widely observed in cancer. Splice variants of cancer-associated genes ... ...

    Abstract AS (alternative splicing) and its role in disease, especially cancer, has come to forefront in research over the last few years. Alterations in the ratio of splice variants have been widely observed in cancer. Splice variants of cancer-associated genes have functions that can alter cellular phenotype, ultimately altering metastatic potential. As metastases are the cause of approximately 90% of all human cancer deaths, it is crucial to understand how AS is dysregulated in metastatic disease. We highlight some recent studies into the relationship between altered AS of key genes and the initiation of prostate cancer metastasis.
    MeSH term(s) Alternative Splicing/genetics ; Animals ; Disease Progression ; Epidermal Growth Factor/genetics ; Epidermal Growth Factor/metabolism ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Male ; Prostatic Neoplasms/genetics ; RNA Splicing/genetics
    Chemical Substances Epidermal Growth Factor (62229-50-9)
    Language English
    Publishing date 2012-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 184237-7
    ISSN 1470-8752 ; 0300-5127
    ISSN (online) 1470-8752
    ISSN 0300-5127
    DOI 10.1042/BST20120026
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  5. Article ; Online: Abscisic acid induced a negative geotropic response in dark-incubated Chlamydomonas reinhardtii.

    Al-Hijab, Layla / Gregg, Adam / Davies, Rhiannon / Macdonald, Heather / Ladomery, Michael / Wilson, Ian

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 12063

    Abstract: The phytohormone abscisic acid (ABA) plays a role in stresses that alter plant water status and may also regulate root gravitropism and hydrotropism. ABA also exists in the aquatic algal progenitors of land plants, but other than its involvement in ... ...

    Abstract The phytohormone abscisic acid (ABA) plays a role in stresses that alter plant water status and may also regulate root gravitropism and hydrotropism. ABA also exists in the aquatic algal progenitors of land plants, but other than its involvement in stress responses, its physiological role in these microorganisms remains elusive. We show that exogenous ABA significantly altered the HCO
    MeSH term(s) Abscisic Acid/metabolism ; Arabidopsis/metabolism ; Arabidopsis/physiology ; Chlamydomonas reinhardtii/metabolism ; Chlamydomonas reinhardtii/physiology ; Chlorophyta/metabolism ; Chlorophyta/physiology ; Gravitropism/physiology ; Light ; Photoperiod ; Plant Growth Regulators/metabolism ; Signal Transduction/genetics ; Stress, Physiological/physiology ; Water/chemistry
    Chemical Substances Plant Growth Regulators ; Water (059QF0KO0R) ; Abscisic Acid (72S9A8J5GW)
    Language English
    Publishing date 2019-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-48632-0
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  6. Article ; Online: CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer.

    Uzor, Simon / Porazinski, Sean R / Li, Ling / Clark, Bethany / Ajiro, Masahiko / Iida, Kei / Hagiwara, Masatoshi / Alqasem, Abdullah A / Perks, Claire M / Wilson, Ian D / Oltean, Sebastian / Ladomery, Michael R

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 7963

    Abstract: Dysregulation of alternative splicing is a feature of cancer, both in aetiology and progression. It occurs because of mutations in splice sites or sites that regulate splicing, or because of the altered expression and activity of splice factors and of ... ...

    Abstract Dysregulation of alternative splicing is a feature of cancer, both in aetiology and progression. It occurs because of mutations in splice sites or sites that regulate splicing, or because of the altered expression and activity of splice factors and of splice factor kinases that regulate splice factor activity. Recently the CDC2-like kinases (CLKs) have attracted attention due to their increasing involvement in cancer. We measured the effect of the CLK inhibitor, the benzothiazole TG003, on two prostate cancer cell lines. TG003 reduced cell proliferation and increased apoptosis in PC3 and DU145 cells. Conversely, the overexpression of CLK1 in PC3 cells prevented TG003 from reducing cell proliferation. TG003 slowed scratch closure and reduced cell migration and invasion in a transwell assay. TG003 decisively inhibited the growth of a PC3 cell line xenograft in nude mice. We performed a transcriptomic analysis of cells treated with TG003. We report widespread and consistent changes in alternative splicing of cancer-associated genes including CENPE, ESCO2, CKAP2, MELK, ASPH and CD164 in both HeLa and PC3 cells. Together these findings suggest that targeting CLKs will provide novel therapeutic opportunities in prostate cancer.
    MeSH term(s) Alternative Splicing/genetics ; Animals ; Apoptosis/drug effects ; Benzothiazoles/pharmacology ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Cyclin-Dependent Kinases/chemistry ; Cyclin-Dependent Kinases/genetics ; Cyclin-Dependent Kinases/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Knockdown Techniques ; Humans ; Male ; Mice, Nude ; Molecular Targeted Therapy ; Neoplasm Invasiveness ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; RNA-Seq ; Thiazoles/pharmacology ; Xenograft Model Antitumor Assays ; Mice
    Chemical Substances Benzothiazoles ; Protein Kinase Inhibitors ; TG 003 ; Thiazoles ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; benzothiazole (G5BW2593EP)
    Language English
    Publishing date 2021-04-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-86908-6
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  7. Article ; Online: Investigating ROS, RNS, and H

    Williams, Eleanor / Whiteman, Matthew / Wood, Mark E / Wilson, Ian D / Ladomery, Michael R / Allainguillaume, Joel / Teklic, Tihana / Lisjak, Miro / Hancock, John T

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 1990, Page(s) 27–42

    Abstract: The modification of proteins is a key way to alter their activity and function. Often thiols, cysteine residues, on proteins are attractive targets for such modification. Assuming that the thiol group is accessible then reactions may take place with a ... ...

    Abstract The modification of proteins is a key way to alter their activity and function. Often thiols, cysteine residues, on proteins are attractive targets for such modification. Assuming that the thiol group is accessible then reactions may take place with a range of chemicals found in cells. These may include reactive oxygen species (ROS), such as hydrogen peroxide (H
    MeSH term(s) Air Pollutants/pharmacology ; Animals ; Arabidopsis/drug effects ; Arabidopsis/growth & development ; Arabidopsis/metabolism ; Arabidopsis Proteins/chemistry ; Arabidopsis Proteins/metabolism ; Caenorhabditis elegans/drug effects ; Caenorhabditis elegans/growth & development ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/chemistry ; Caenorhabditis elegans Proteins/metabolism ; Hydrogen Sulfide/pharmacology ; Protein Processing, Post-Translational ; Reactive Nitrogen Species/pharmacology ; Reactive Oxygen Species/pharmacology ; Sulfhydryl Compounds/chemistry
    Chemical Substances Air Pollutants ; Arabidopsis Proteins ; Caenorhabditis elegans Proteins ; Reactive Nitrogen Species ; Reactive Oxygen Species ; Sulfhydryl Compounds ; Hydrogen Sulfide (YY9FVM7NSN)
    Language English
    Publishing date 2019-05-24
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9463-2_3
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  8. Article ; Online: Conjugated linoleate reduces prostate cancer viability whereas the effects of oleate and stearate are cell line-dependent.

    Hagen, Rachel M / Rhodes, Anthony / Ladomery, Michael R

    Anticancer research

    2013  Volume 33, Issue 10, Page(s) 4395–4400

    Abstract: Background: In this study, responses to fatty acid treatments in commonly used prostate cancer cell culture models and variability of gene expression between them were determined.: Materials and methods: PC3, DU145, LNCaP, VCaP and PNT2 cells were ... ...

    Abstract Background: In this study, responses to fatty acid treatments in commonly used prostate cancer cell culture models and variability of gene expression between them were determined.
    Materials and methods: PC3, DU145, LNCaP, VCaP and PNT2 cells were treated with 100 μM of either oleate, stearate or conjugated linoleate. Cell proliferation and viability were assessed using trypan blue and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay respectively. Gene expression was measured using real-time polymerase chain reaction (PCR).
    Results: Conjugated linoleic acid reduced cell proliferation and viability in all prostate cancer cell lines, whilst the effects of oleic and stearic acid on proliferation were found to be cell line-dependent. A reduction in gene expression of fatty acid desaturases was observed in prostate cancer cell lines compared to normal prostate cells.
    Conclusion: Differential responses of the cell lines investigated here to fatty acid treatment suggest that multiple prostate cancer cell line models should be used when designing experiments aimed at examining lipid metabolism in prostate cancer.
    MeSH term(s) Acetyl-CoA Carboxylase/genetics ; Acetyl-CoA Carboxylase/metabolism ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Screening Assays, Antitumor ; Fatty Acid Synthase, Type I/genetics ; Fatty Acid Synthase, Type I/metabolism ; Gene Expression/drug effects ; Glycerol-3-Phosphate O-Acyltransferase/genetics ; Glycerol-3-Phosphate O-Acyltransferase/metabolism ; Humans ; Linoleic Acids, Conjugated/pharmacology ; Lipid Metabolism/drug effects ; Lipid Metabolism/genetics ; Male ; Oleic Acid/pharmacology ; PPAR gamma/genetics ; PPAR gamma/metabolism ; Prostatic Neoplasms ; Stearic Acids/pharmacology
    Chemical Substances Antineoplastic Agents ; Linoleic Acids, Conjugated ; PPAR gamma ; Stearic Acids ; Oleic Acid (2UMI9U37CP) ; stearic acid (4ELV7Z65AP) ; Glycerol-3-Phosphate O-Acyltransferase (EC 2.3.1.15) ; FASN protein, human (EC 2.3.1.85) ; Fatty Acid Synthase, Type I (EC 2.3.1.85) ; Acetyl-CoA Carboxylase (EC 6.4.1.2)
    Language English
    Publishing date 2013-10
    Publishing country Greece
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604549-2
    ISSN 1791-7530 ; 0250-7005
    ISSN (online) 1791-7530
    ISSN 0250-7005
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    Zs.A 1642: Show issues Location:
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  9. Article: The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties.

    Jumbe, Samantha L / Porazinski, Sean R / Oltean, Sebastian / Mansell, Jason P / Vahabi, Bahareh / Wilson, Ian D / Ladomery, Michael R

    Translational oncology

    2018  Volume 12, Issue 1, Page(s) 134–142

    Abstract: The oncogene ERG encodes an ETS family transcription factor and is implicated in blood, vascular, and bone development and in prostate, blood, and bone cancer. The ERG gene is alternatively spliced; of particular interest is its cassette exon 7b which ... ...

    Abstract The oncogene ERG encodes an ETS family transcription factor and is implicated in blood, vascular, and bone development and in prostate, blood, and bone cancer. The ERG gene is alternatively spliced; of particular interest is its cassette exon 7b which adds 24 amino acids, in frame, to the transcriptional activation domain. Higher exon 7b inclusion rates are associated with increased cell proliferation and advanced prostate cancer. The 24 amino acids encoded by exon 7b show evolutionary conservation from humans to echinoderms, highlighting their functional importance. Throughout evolution, these 24 amino acids are encoded by a distinct short exon. Splice-switching oligonucleotides based on morpholino chemistry were designed to induce skipping of ERG exon 7b in MG63 osteosarcoma and VCaP prostate cancer cells. Induction of exon 7b skipping reduced cell proliferation and invasion, increased apoptosis in vitro, and reduced xenograft growth in vivo. We also show that ERG's exon 7b is required for the induction of tissue nonspecific alkaline phosphatase. Together, these findings show that the evolutionarily conserved cassette exon 7b is central to ERG's oncogenic properties.
    Language English
    Publishing date 2018-10-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2443840-6
    ISSN 1936-5233 ; 1936-5233 ; 1944-7124
    ISSN (online) 1936-5233
    ISSN 1936-5233 ; 1944-7124
    DOI 10.1016/j.tranon.2018.09.001
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  10. Article: The oncogenic transcription factor ERG represses the transcription of the tumour suppressor gene

    Adamo, Patricia / Porazinski, Sean / Rajatileka, Shavanthi / Jumbe, Samantha / Hagen, Rachel / Cheung, Man-Kim / Wilson, Ian / Ladomery, Michael R

    Oncology letters

    2017  Volume 14, Issue 5, Page(s) 5605–5610

    Abstract: The oncogene ETS-related gene (ERG) encodes a transcription factor with roles in the regulation of haematopoiesis, angiogenesis, vasculogenesis, inflammation, migration and invasion. ... ...

    Abstract The oncogene ETS-related gene (ERG) encodes a transcription factor with roles in the regulation of haematopoiesis, angiogenesis, vasculogenesis, inflammation, migration and invasion. The
    Language English
    Publishing date 2017-08-28
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 2573196-8
    ISSN 1792-1082 ; 1792-1074
    ISSN (online) 1792-1082
    ISSN 1792-1074
    DOI 10.3892/ol.2017.6841
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