1. Context-specific microRNA analysis: identification of functional microRNAs and their mRNA targets.

    Nucleic Acids Research 40(21):10614 (2012) PMID 22977182 PMCID PMC3505984

    MicroRNAs (miRs) function primarily as post-transcriptional negative regulators of gene expression through binding to their mRNA targets. Reliable prediction of a miR's targets is a considerable bioinformatic challenge of great importance for inferring the miR's function. Sequence-based predicti...
  2. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours.

    Embo Molecular Medicine 4(11):1214 (2012) PMID 23125021 PMCID PMC3494877

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequ...
  3. EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF.

    FASEB Journal 26(4):1582 (2012) PMID 22198386 PMCID PMC3316897

    The signaling pathways that commit cells to migration are incompletely understood. We employed human mammary cells and two stimuli: epidermal growth factor (EGF), which induced cellular migration, and serum factors, which stimulated cell growth. In addition to strong activation of ERK by EGF, an...
  4. EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF.

    FASEB Journal 26(4):1582 (2012) PMID 22198386 PMCID PMC3316897

    The signaling pathways that commit cells to migration are incompletely understood. We employed human mammary cells and two stimuli: epidermal growth factor (EGF), which induced cellular migration, and serum factors, which stimulated cell growth. In addition to strong activation of ERK by EGF, an...
  5. A crossroad of microRNAs and immediate early genes (IEGs) encoding oncogenic transcription factors in breast cancer.

    Journal of Mammary Gland Biology and Neoplasia 17(1):3 (2012) PMID 22327345

    Signaling networks are involved in development, as well as in malignancy of the mammary gland. Distinct external stimuli activate intricate signaling cascades, which culminate in the activation of specific transcriptional programs. These signal-specific transcriptional programs are instigated by...
  6. Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor.

    Molecular Cancer 11:44 (2012) PMID 22747855 PMCID PMC3444916

    Metastatic melanoma is a devastating disease with limited therapeutic options. MicroRNAs (miRNAs) are small non coding RNA molecules with important roles in post-transcriptional gene expression regulation, whose aberrant expression has been implicated in cancer. We show that the expression of mi...
  7. Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals.

    Molecular Cell 42(4):524 (2011) PMID 21596316 PMCID PMC3100487

    Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse,...
  8. Two Phases of Mitogenic Signaling Unveil Roles for p53 and EGR1 in Elimination of Inconsistent Growth Signals

    Molecular Cell 42(4):524 (2011)

    Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second p...
  9. Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity.

    PLoS ONE 6(4):e19246 (2011) PMID 21559428 PMCID PMC3084788

    In leukemia patients, stress and anxiety were suggested to predict poorer prognosis. Oncological patients experience ample physiological and psychological stress, potentially leading to increased secretion of stress factors, including epinephrine, corticosteroids, and prostaglandins. Here we tes...
  10. Synergism between immunostimulation and prevention of surgery-induced immune suppression: An approach to reduce post-operative tumor progression

    Brain, Behavior, and Immunity 24(6):952 (2010)

    Background: A unique opportunity to eradicate cancer is presented immediately after the excision of the primary tumor, but surgical procedures often induce the release of immunosuppressing factors that render cell mediated immunity ineffective. Here we tested the hypothesis that integr...
  11. Synergism between immunostimulation and prevention of surgery-induced immune suppression: an approach to reduce post-operative tumor progression.

    Brain, Behavior, and Immunity 24(6):952 (2010) PMID 20362661 PMCID PMC2897966

    A unique opportunity to eradicate cancer is presented immediately after the excision of the primary tumor, but surgical procedures often induce the release of immunosuppressing factors that render cell mediated immunity ineffective. Here we tested the hypothesis that integration of peri-operativ...
  12. EGF decreases the abundance of microRNAs that restrain oncogenic transcription factors.

    Science Signaling 3(124):ra43 (2010) PMID 20516477

    Epidermal growth factor (EGF) stimulates cells by launching gene expression programs that are frequently deregulated in cancer. MicroRNAs, which attenuate gene expression by binding complementary regions in messenger RNAs, are broadly implicated in cancer. Using genome-wide approaches, we showed...
  13. Synergism between immunostimulation and prevention of surgery-induced immune suppression: An approach to reduce post-operative tumor progression

    Brain, Behavior, and Immunity 24(6):952 (2010)

    Background: A unique opportunity to eradicate cancer is presented immediately after the excision of the primary tumor, but surgical procedures often induce the release of immunosuppressing factors that render cell mediated immunity ineffective. Here we tested the hypothesis that inte...
  14. Blood transfusion promotes cancer progression: a critical role for aged erythrocytes.

    Anesthesiology 109(6):989 (2008) PMID 19034095 PMCID PMC2694914

    In cancer patients, allogeneic blood transfusion is associated with poorer prognosis, but the independent effect of the transfusion is controversial. Moreover, mediating mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of dono...
  15. Perioperative use of beta-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis.

    Annals of Surgical Oncology 15(7):2042 (2008) PMID 18398660 PMCID PMC3872002

    COX inhibitors and beta-blockers were recently suggested to reduce cancer progression through inhibition of tumor proliferation and growth factor secretion, induction of tumor apoptosis, and prevention of cellular immune suppression during the critical perioperative period. Here we evaluated the...
  16. Prophylactic IL-12 treatment reduces postoperative metastasis: mediation by increased numbers but not cytotoxicity of NK cells.

    Breast Cancer Research and Treatment 107(2):211 (2008) PMID 17431763

    Despite a promising potential, interleukin-12 immunotherapy has yielded limited clinical success while causing perilous toxicities. Here we study a context in which IL-12 may prove clinically beneficial--the removal of the primary tumor, when cell-mediated immunity (CMI) may eradicate minimal re...
  17. Prophylactic IL-12 treatment reduces postoperative metastasis: mediation by increased numbers but not cytotoxicity of NK cells.

    Breast Cancer Research and Treatment 107(2):211 (2008) PMID 17431763

    Despite a promising potential, interleukin-12 immunotherapy has yielded limited clinical success while causing perilous toxicities. Here we study a context in which IL-12 may prove clinically beneficial--the removal of the primary tumor, when cell-mediated immunity (CMI) may eradicate minimal re...
  18. A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration.

    Nature Cell Biology 9(8):961 (2007) PMID 17643115

    Cell migration driven by the epidermal growth factor receptor (EGFR) propels morphogenesis and involves reorganization of the actin cytoskeleton. Although de novo transcription precedes migration, transcript identity remains largely unknown. Through their actin-binding domains, tensins link the ...
  19. A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration.

    Nature Cell Biology 9(8):961 (2007) PMID 17643115

    Cell migration driven by the epidermal growth factor receptor (EGFR) propels morphogenesis and involves reorganization of the actin cytoskeleton. Although de novo transcription precedes migration, transcript identity remains largely unknown. Through their actin-binding domains, tensins link the ...
  20. Immune suppression while awaiting surgery and following it: dissociations between plasma cytokine levels, their induced production, and NK cell cytotoxicity.

    Brain, Behavior, and Immunity 21(4):503 (2007) PMID 17293081

    Surgery may render patients susceptible to life-threatening complications, including infections and later metastases. Suppression of cell mediated immunity (CMI) and perturbations in the cytokine network were implicated in these outcomes. The current study assessed the effects of various surgeri...