Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    Language: English
    In: Cancer research, 15 December 2017, Vol.77(24), pp.6818-6824
    Description: Mutations in the gene have been associated with chemotherapy resistance and poor prognosis in patients with acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia, and myelodysplastic syndromes. However, the underlying mechanisms connecting RUNX1 to the success of therapy remain elusive. Here we explore the hypothesis that RUNX1 is directly involved in the response of hematopoietic cells to cytotoxic agents. RUNX1 was upregulated posttranscriptionally by cytotoxic agents in C57BL/6 mice and hematopoietic cell lines. Upregulation was also seen in primary human AML cells after treatment with cytarabine Upon overexpression, RUNX1 restricted proliferation, promoted apoptosis, and augmented the DNA damage response. This unknown activity of RUNX1 required an intact runt homology domain (RHD), a domain where most leukemia-associated point mutations cluster. Consistent with this, two RHD-defective RUNX1 proteins lacked any antiproliferative or apoptotic activity, and RHD-defective (K83N, N109D) mutant RUNX1 conferred resistance to ionizing radiation when overexpressed in Ba/F3 cells under certain conditions. Our experiments reveal a novel function of RUNX1 and offer an explanation for the link between mutations and chemotherapy and radiation resistance. Moreover, these data suggest that pharmacologic modulation of RUNX1 might be an attractive new approach to treat hematologic malignancies. .
    Keywords: Apoptosis -- Drug Effects ; Core Binding Factor Alpha 2 Subunit -- Genetics ; Cytotoxins -- Pharmacology
    ISSN: 00085472
    E-ISSN: 1538-7445
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Archives of Toxicology, 2015, Vol.89(4), pp.501-517
    Description: The tumour suppressor p53 is a central player in cellular DNA damage responses. P53 is upregulated and activated by genotoxic stress and induces a transcriptional programme with effectors promoting apoptosis, cell cycle arrest, senescence and DNA repair. For the best part of the last three decades, these DNA damage-related programmes triggered by p53 were unequivocally regarded as the major if not sole mechanism by which p53 exerts its tumour suppressor function. However, this interpretation has been challenged by a number of recent in vivo studies, demonstrating that mice which are defective in inducing p53-dependent apoptosis, cell cycle arrest and senescence suppress thymic lymphoma as well as wild-type p53 expressing animals. Consequently, the importance of DNA damage responses for p53-mediated tumour suppression has been questioned. In this review, I summarize current knowledge on p53-controlled DNA damage responses and argue that these activities, while their role has certainly changed, remain an important feature of p53 biology with relevance for cancer therapy and tumour suppression.
    Keywords: P53 ; DNA damage ; Tumour suppression ; Cancer therapy ; Apoptosis ; Cell cycle arrest ; Senescence ; DNA Repair
    ISSN: 0340-5761
    E-ISSN: 1432-0738
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Trends in Molecular Medicine, 2011, Vol.17(3), pp.117-118
    Keywords: Medicine ; Biology
    ISSN: 1471-4914
    E-ISSN: 1471-499X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Trends in Cell Biology, January 2010, Vol.20(1), pp.14-24
    Description: Apoptosis induced by p53 is firmly established as a central mechanism of tumour suppression. In addition to its complex functions as a nuclear transcription factor, p53 can act in the cytosol and mitochondria to promote apoptosis through transcription-independent mechanisms. Recent studies have shown that physical and functional interactions of p53 with various members of the Bcl-2 family provide the basis for this alternative route of p53-mediated cell death. However, different models of how these interactions promote apoptosis have been proposed. This review focuses on the mechanisms, regulation and physiological roles of transcription-independent p53 activities and highlights recent findings suggesting that the utilisation of these activities provides a promising alternative strategy for p53-based cancer therapy.
    Keywords: Biology
    ISSN: 0962-8924
    E-ISSN: 1879-3088
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Frontiers in oncology, 2014, Vol.4, pp.304
    Description: In response to stress, cells activate so-called checkpoints – complex signaling pathways that induce a plethora of cellular outcomes. Checkpoints primarily initiate cell cycle arrest to provide the cell with time to repair the damage. However, if the damage is too severe then cells can permanently arrest the cell cycle (senescence) or trigger cell death, thereby preventing the transmission of genetic defects. These responses are pivotal for tumor suppression as all of these outcomes result in restriction of the growth and/or elimination of damaged and pre-malignant cells. Thus, a large number of anti-cancer agents target specific components of stress response signaling pathways with the aim of causing tumor regression by stimulating cell death or at least stopping cell growth. However, the efficacy of these agents is often impaired by mutations in genes that are involved in stress-responsive signaling pathways. Moreover, these cancer-specific genetic defects often contribute to resistance against chemotherapeutic agents and/or radiotherapy. Modulating the outcome of cellular stress responses toward cell death in tumor cells without affecting surrounding normal cells is thus one of the ultimate aims in the development of new cancer therapeutics. To achieve this aim, a detailed understanding of cellular stress response pathways and their aberrations in cancer is required.
    Keywords: DNA Damage ; DNA Repair ; Apoptosis ; Cellular Stress ; Chemotherapy ; Therapeutic Targets ; Therapy Resistance ; Tumorigenesis
    ISSN: 2234-943X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Current protocols in cytometry, April 2011, Vol.Chapter 7, pp.Unit 7.39
    Description: This unit describes an easy, rapid, and universal procedure to process fresh and nitrogen-frozen tissue specimens for high-resolution cell cycle and DNA ploidy analysis. Unlike other protocols, this procedure does not require treating tissues with enzymes, detergents, or other plasma membrane-lysing chemicals, but it achieves tissue dispersion by a simple two-step mechanical process that can be performed in ∼5 min. Resulting single-cell suspensions are fixed with ethanol, stained with propidium iodide, and subjected to flow cytometric DNA content analysis. The method can be applied without any alterations to all tissue types (except bones) derived from several species and results in highly reproducible cell cycle profiles of excellent resolution. The described protocol can be used to reliably and accurately detect subtle cell cycle and ploidy alterations in tissue specimens, including cell cycle arrest, aneuploidy, and apoptosis/necrosis-associated DNA fragmentation.
    Keywords: Cell Cycle ; Organ Specificity ; Ploidies ; Cytological Techniques -- Methods
    ISSN: 19349297
    E-ISSN: 1934-9300
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Cell Cycle, 15 September 2010, Vol.9(18), pp.3847-3849
    Keywords: Biology
    ISSN: 1538-4101
    E-ISSN: 1551-4005
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Mammalian Genome, 2018, Vol.29(11), pp.691-693
    Keywords: Genomes ; Cancer;
    ISSN: 0938-8990
    E-ISSN: 1432-1777
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Biochemical Society transactions, August 2014, Vol.42(4), pp.752-7
    Description: Various experimental strategies aim to (re)activate p53 signalling in cancer cells. The most advanced clinically are small-molecule inhibitors of the autoregulatory interaction between p53 and MDM2 (murine double minute 2). Different MDM2 inhibitors are currently under investigation in clinical trials. As for other targeted anti-cancer therapy approaches, relatively rapid resistance acquisition may limit the clinical efficacy of MDM2 inhibitors. In particular, MDM2 inhibitors were shown to induce p53 mutations in experimental systems. In the present article, we summarize what is known about MDM2 inhibitors as anti-cancer drugs with a focus on the acquisition of resistance to these compounds.
    Keywords: Antineoplastic Agents -- Therapeutic Use ; Neoplasms -- Drug Therapy ; Proto-Oncogene Proteins C-Mdm2 -- Antagonists & Inhibitors
    ISSN: 03005127
    E-ISSN: 1470-8752
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Cell Cycle, 01 September 2010, Vol.9(17), pp.3584-3590
    Description: Cell cycle alterations are fundamental to many physiological processes but their detection has proven difficult when cells are in the context of a tissue structure. Here we describe an easy, rapid and optimization-free procedure for obtaining high resolution cell cycle profiles from nearly...
    Keywords: Biology
    ISSN: 1538-4101
    E-ISSN: 1551-4005
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages