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Of Malignancies (of + malignancy)

Distribution by Scientific Domains
Medical Sciences71%
Life Sciences28%

Kinds of Of Malignancies

  • variety of malignancy
    		•

    Selected Abstracts

    Regulation of Wnt/,-catenin signaling by protein kinases

    DEVELOPMENTAL DYNAMICS, Issue 1 2010
    Esther M. Verheyen
    Abstract The Wnt/,-catenin signaling pathway plays essential roles during development and adult tissue homeostasis. Inappropriate activation of the pathway can result in a variety of malignancies. Protein kinases have emerged as key regulators at multiple steps of the Wnt pathway. In this review, we present a synthesis covering the latest information on how Wnt signaling is regulated by diverse protein kinases. Developmental Dynamics 239:34,44, 2010. © 2009 Wiley-Liss, Inc. [source]

    ABCG2 (BCRP) expression in normal and malignant hematopoietic cells

    HEMATOLOGICAL ONCOLOGY, Issue 3 2003
    Brian L. Abbott
    Abstract ABCG2 (BCRP) is a member of the ATP-binding cassette (ABC) family of cell surface transport proteins. ABCG2 expression occurs in a variety of normal tissues, and is relatively limited to primitive stem cells. ABCG2 expression is associated with the side population (SP) phenotype of Hoechst 33342 efflux. The substrate profile of ABCG2 includes the antineoplastic drugs primarily targeting topoisomerases, including anthracyclines and camptothecins. More recently, pheophorbide, a chlorophyll-breakdown product, and protoporhyrin IX have been described as ABCG2 substrates, perhaps indicating a physiologic role of cytoprotection of primitive cells. Also, mice lacking ABCG2 expression have no intrinsic stem cell defects, although there is a remarkable increase in toxicity with antineoplastic drugs that are ABCG2 substrates, and also a photosensitivity resembling protoporphyria. Like other members of the ABC family, such as MDR1 and MRP1, ABCG2 is expressed in a variety of malignancies. Despite numerous reports of ABCG2 expression in AML, there is little evidence that ABCG2 expression is correlated with an adverse clinical outcome. This review will focus on the potential usefulness of ABCG2 as a marker primitive stem cells and possible physiologic roles of ABCG2 in protection of primitive stem cell populations, and potential methods of overcoming ABCG2-associated drug resistance in anticancer therapy. Copyright © 2003 John Wiley & Sons, Ltd. [source]

    Diethylstilbestrol effects and lymphomagenesis in Mlh1 -deficient mice

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2005
    Omar Kabbarah
    Abstract Inherited defects in DNA mismatch repair (MMR) predispose to a variety of malignancies in humans and in mouse knockout models. In humans, hemizygosity for one of several DNA MMR genes greatly increases an individual's risk for colon and endometrial carcinoma. Hemizygous mice develop gastrointestinal tumors at a low to moderate frequency. Homozygous nulls have higher rates of gastrointestinal tumors and are particularly susceptible to lymphoma. In an effort to model endometrial carcinoma associated with mutation in MMR, we treated mice carrying knockout alleles for Mlh1 or Msh2 with the synthetic estrogen diethylstilbestrol (DES), a known promoter of uterine endometrial carcinoma. The C57BL/6 mice carrying DNA MMR mutations failed to develop endometrial carcinomas. However, the Mlh1 -deficient mice treated with DES tended to become moribund at an early age and had very early onset of lymphoma. Comparison of DES-treated and untreated Mlh1,/, animals suggests the combination of Mlh1 deficiency and DES exposure accelerates lymphomagenesis. © 2005 Wiley-Liss, Inc. [source]

    PARP1 expression in pediatric central nervous system tumors,

    PEDIATRIC BLOOD & CANCER, Issue 7 2009
    Valerie N. Barton BA
    Abstract Background Despite advances in therapy, outcome in many high-grade pediatric central nervous system (CNS) tumors remains poor. The focus of neuro-oncology research has thus turned towards identifying novel therapeutic targets. Poly(ADP-ribose) polymerase-1 (PARP1) is a DNA repair protein that has been studied in a variety of malignancies and may interfere with therapy-induced DNA damage, however expression in pediatric CNS tumors is unknown. Procedure We evaluated PARP1 mRNA expression in 81 pediatric CNS tumors using microarray technology. Protein expression was examined by Western blot. Results PARP1 mRNA is highly expressed in high-grade tumors (P,<,0.0001). PARP1 mRNA expression was greater in high-grade glioma than pilocytic astrocytoma (P,=,3.5,×,10,5) and in large cell medulloblastoma over classic medulloblastoma (P,=,0.0053). PARP1 protein was also prominent in high-grade tumors (P,=,0.022). Conclusion These findings indicate that PARP1 is expressed in high-grade pediatric CNS tumors, implicating PARP1 inhibition as a potential therapeutic target. Pediatr Blood Cancer 2009; 53:1227,1230. © 2009 Wiley-Liss, Inc. [source]

    Seroreactivity against MAGE-A and LAGE-1 proteins in melanoma patients

    BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003
    D. Usener
    Summary Background Cancer-testis antigens exemplify a growing number of tumour antigens which are expressed in a variety of malignancies, but not in normal tissues other than germ cells, primarily those of the testis. Objectives To investigate the humoral response to known cancer-testis antigens in melanoma patients. Methods We used phage clones coding for seven different melanoma antigens MAGE-A or LAGE-1A proteins. These clones were isolated using the newly developed DNA hybridization analysis of recombinantly expressed cDNA libraries (HYREX) approach. HYREX combines the advantage of a nonradioactive library screening method with the possibility of subsequently analysing the serological response to the recombinant proteins. We isolated clones coding for MAGE-A1, -A3, -A4b, -A6, -A9 and -A12, as well as LAGE-1A. Additionally, we correlated gene expression and seroreactivity. Results Between 13% and 27% of sera (n = 15) were reactive against individual tumour antigens. We found the presence of specific antibodies was, with only two exceptions, generally correlated with mRNA expression of the antigen within cell lines derived from the same patient. While cross-reactivity of patients' IgG might play a role in these cases, antibodies from patients' sera were able to distinguish even the closely related MAGE-A3 and -A6. In general, the mRNA expression frequency was higher than the detected IgG responses. Conclusions Antibody recognition of specific tumour antigens by patients' sera may be used for evaluating the possible immunogenicity of new antigens; serological tests could be used for tumour monitoring purposes. [source]

    Signal transduction of inflammatory cytokines and tumor development

    CANCER SCIENCE, Issue 6 2006
    Akihiko Yoshimura
    It has been estimated that >20% of all malignancies are initiated or exacerbated by inflammation. Until recently, the molecular basis of this process has not been clarified. However, recent studies have uncovered the molecular mechanism of intracellular signaling pathways of inflammatory cytokines such as tumor necrosis factor (TNF)-,, interferon (IFN)-, and interleukin (IL)-6. Three major transcription factors including NF-,B, STAT1 and STAT3 have been shown to play major roles in transmitting inflammatory cytokine signals to the nucleus. One function of NF-,B and STAT3 in tumor cells is the promotion of cell growth and cell survival through the induction of target genes, whose products promote cell division and inhibit apoptosis. In addition, NF-,B and STAT1 are important transcription factors that induce inflammatory mediators from inflammatory cells, especially macrophages, while STAT3 often antagonizes this process. STAT1 is generally believed to be an anti-oncogene because it promotes apoptosis through p53, but it could promote inflammation-mediated tumor development by enhancing tissue injury, remodeling, fibrosis and inflammation. Hence, the inhibition of NF-,B and STATs offers a strategy for treatment of a variety of malignancies and can convert inflammation-induced tumor growth into inflammation-induced tumor regression. (Cancer Sci 2006; 97) [source]

    Human Heart Cytosolic Reductases and Anthracycline Cardiotoxicity

    IUBMB LIFE, Issue 1 2001
    Alvaro Mordente
    Abstract Anthracyclines are a class of antitumor drugs widely used for the treatment of a variety of malignancy, including leukemias, lymphomas, sarcomas, and carcinomas. Different mechanisms have been proposed for anthracycline antitumor effects including freeradical generation, DNA intercalation/binding, activation of signaling pathways, inhibition of topoisomerase II and apoptosis. A life-threatening form of cardiomyopathy hampers the clinical use of anthracyclines. According to the prevailing hypothesis, anthracyclines injure the heart by generating damaging free radicals through iron-catalyzed redox cycling. Although the "iron and freeradical hypothesis" can explain some aspects of anthracycline acute toxicity, it is nonetheless disappointing when referred to chronic cardiomyopathy. An alternative hypothesis implicates C-13 alcohol metabolites of anthracyclines as mediators of myocardial contractile dysfunction ("metabolite hypothesis"). Hydroxy metabolites are formed upon two-electron reduction of the C-13 carbonyl group in the side chain of anthracyclines by cytosolic NADPH-dependent reductases. Anthracycline alcohol metabolites can affect myocardial energy metabolism, ionic gradients, and Ca 2+ movements, ultimately impairing cardiac contraction and relaxation. In addition, alcohol metabolites can impair cardiac intracellular iron handling and homeostasis, by delocalizing iron from the [4Fe-4S] cluster of cytoplasmic aconitase. Chronic cardiotoxicity induced by C-13 alcohol metabolite might be primed by oxidative stress generated by anthracycline redox cycling ("unifying hypothesis"). Putative cardioprotective strategies should be aimed at decreasing C-13 alcohol metabolite production by means of efficient inhibitors of anthracycline reductases, as short-chain coenzyme Q analogs and chalcones that compete with anthracyclines for the enzyme active site, or by developing novel anthracyclines less susceptible to reductive metabolism. [source]